Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy

Ilić, Violeta; Bogićević, Dragana; Miljković, Branislava; Jesic, Maja; Kovačević, Marijana; Prostran, Milica; Kovačević, Sandra Vezmar

doi:10.1684/epd.2016.0821

Cited by 9 publications

(6 citation statements)

References 22 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Vainionpaa et al demonstrated a reversal of raised TSH levels after discontinuation of the medication [ 14 ]. There was no association between serum valproate level and subclinical hypothyroidism, as in previous studies [ 6 , 15 ]. Though Kim et al demonstrated an association between valproate levels and subclinical hypothyroidism [ 13 ].…”

Section: Discussionsupporting

confidence: 75%

Effect of Valproate Monotherapy on Thyroid Function Tests and Magnesium Levels in Children With Epilepsy

Alhyan,

Aggarwal,

Chhillar

et al. 2023

Cureus

View full text Add to dashboard Cite

Background: Antiseizure drug valproate alters thyroid functions. Magnesium is implicated in the pathogenesis of epilepsy and it may affect the efficacy of valproate and thyroid functions. Objective: To study the effect of six months of valproate monotherapy on thyroid functions and serum magnesium levels. To study the association among these levels and the effects of clinicodemographic profile. Materials and method: Children aged three to 12 years presenting with newly diagnosed epilepsy were enrolled. A venous blood sample was collected for estimation of thyroid function test (TFT), magnesium, and valproate levels at onset and after six months of valproate monotherapy. Valproate levels and TFT were analyzed by chemiluminescence and magnesium by colorimetric method. Results: Thyroid stimulating hormone (TSH) increased significantly from 2.14±1.64 µIU/ml at enrollment to 3.64±2.15 µIU/ml at six months (p<0.001), free thyroxine (FT4) decreased significantly (p<0.001). Serum magnesium (Mg) decreased from 2.30±0.29 mg/dl to 1.94±0.28 mg/dl (p<0.001). At six months, eight out of 45 (17.77%) participants had significantly increased mean TSH levels (p=0.008). Serum valproate levels were not associated significantly with TFT and Mg (p<0.05). There was no effect of age, sex, or repeat seizures on the measured parameters. Conclusion: The TFT and Mg levels are altered by six months of valproate monotherapy in children with epilepsy. Hence we suggest monitoring and supplementation if required.

show abstract

Section: Discussionsupporting

confidence: 75%

Effect of Valproate Monotherapy on Thyroid Function Tests and Magnesium Levels in Children With Epilepsy

Alhyan,

Aggarwal,

Chhillar

et al. 2023

Cureus

View full text Add to dashboard Cite

show abstract

“…8,9,14,17 Yet other studies reported similar results to ours, showing an increase in TSH with normal fT4 levels. 18,19 In our study, we detected subclinical hypothyroidism in 16% of the children receiving VPA treatment, and none in the LEV group. Our results duplicate those previously reported in the literature which found a 12.5 to 28% frequency of subclinical hypothyroidism in children receiving VPA.…”

Section: Discussionsupporting

confidence: 49%

“…Our results duplicate those previously reported in the literature which found a 12.5 to 28% frequency of subclinical hypothyroidism in children receiving VPA. 9,14,18 AEDs might cause thyroid dysfunction via several mechanisms such as disturbing its biosynthesis, secretion, transport, metabolism, and excretion. 3,20 One of the most important mechanisms is the hepatic enzyme induction of the AEDs such as phenytoin and carbamazepine that increase the metabolism of thyroid hormones.…”

Section: Discussionmentioning

confidence: 99%

Thyroid Functions in Children on Levetiracetam or Valproic Acid Therapy

Karatoprak

Paksoy

2020

Journal of Pediatric Epilepsy

View full text Add to dashboard Cite

The aim of this study was to investigate the thyroid functions in children receiving levetiracetam or valproate monotherapy. We retrospectively reviewed the records of children with controlled epilepsy receiving valproic acid (VPA group) or levetiracetam monotherapy (LEV group) for at least 6 months. Free thyroxine 4 levels (fT4) and thyroid stimulating hormone (TSH) levels were compared between VPA group, LEV group, and age- and gender-matched healthy children (control group). A total of 190 children were included in the study: 63 were in the VPA, 60 in the LEV, and 67 in the control group. Although there was no significant difference regarding average fT4 levels, higher TSH levels were found in the VPA group when compared with the LEV and control groups (p < 0.001 and p < 0.001, respectively). There was no significant difference in terms of fT4 and TSH values in the LEV group when compared with the control group (p = 0.56 and p = 0.61, respectively). Subclinical hypothyroidism (defined as a TSH level above 5 uIU/mL with a normal fT4 level was detected in 16% of patients in the VPA group, none in the LEV and control groups. Our study found that VPA therapy is associated with an increased risk of subclinical hypothyroidism while LEV had no effect on thyroid function tests.

show abstract

“…In contrast with the observation by Yilmaz et al, we did not observe a decrease in frequency of subclinical hypothyroidism in patients receiving LEV. The duration of ASD therapy, age, daily dosage, and serum level of ASDs could be potential risk factors for thyroid dysfunction . Assessment of thyroid function in epileptic children would be helpful, because ASDs could influence thyroid dysfunction and development of subclinical hypothyroidism.…”

Section: Discussionmentioning

confidence: 99%

Analysis of antiseizure drug‐related adverse reactions from the electronic health record using the common data model

Choi

Kim

et al. 2020

Epilepsia

View full text Add to dashboard Cite

Objective: Antiseizure drugs (ASDs) are known to cause a wide range of adverse drug reactions (ADRs). Recently, electronic health care data using the common data model (CDM) have been introduced and commonly adopted in pharmacovigilance research. We aimed to analyze ASD-related ADRs using CDM and to assess the feasibility of CDM analysis in monitoring ADR in a single tertiary hospital. Methods: We selected five ASDs: oxcarbazepine (OXC), lamotrigine (LTG), levetiracetam (LEV), valproic acid (VPA), and topiramate (TPM). Patients diagnosed with epilepsy and exposed to monotherapy with one of the ASDs before age 18 years were included. We measured four ADR outcomes: (1) hematologic abnormality, (2) hyponatremia, (3) elevation of liver enzymes, and (4) subclinical hypothyroidism. We performed a subgroup analysis to exclude the effects of concomitant medications. Results: From the database, 1344 patients were included for the study. Of the 1344 patients, 436 were receiving OXC, 293 were receiving LTG, 275 were receiving LEV, 180 were receiving VPA, and 160 were receiving TPM. Thrombocytopenia developed in 14.1% of patients taking VPA. Hyponatremia occurred in 10.5% of patients taking OXC. Variable ranges of liver enzyme elevation were detected in 19.3% of patients taking VPA. Subclinical hypothyroidism occurred in approximately 21.5% to 28% of patients with ASD monotherapy, which did not significantly differ according to the type of ASD. In a subgroup analysis, we observed similar ADR tendencies, but with less thrombocytopenia in the TPM group. Significance: The incidence and trends of ADRs that were evaluated by CDM were similar to the previous literature. CDM can be a useful tool for analyzing ASDrelated ADRs in a multicenter study. The strengths and limitations of CDM should be carefully addressed. K E Y W O R D Sadverse drug reaction, antiseizure drugs, common data model, epilepsy, pharmacovigilance | 611 CHOI et al.

show abstract

Duration of valproic acid monotherapy correlates with subclinical thyroid dysfunction in children with epilepsy

Cited by 9 publications

References 22 publications

Effect of Valproate Monotherapy on Thyroid Function Tests and Magnesium Levels in Children With Epilepsy

Effect of Valproate Monotherapy on Thyroid Function Tests and Magnesium Levels in Children With Epilepsy

Thyroid Functions in Children on Levetiracetam or Valproic Acid Therapy

Analysis of antiseizure drug‐related adverse reactions from the electronic health record using the common data model

Contact Info

Product

Resources

About