Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Doneray, Hakan; Kara, İlknur Sürücü; Karakoc, Akar; Tan, Hüseyin; Orbak, Zerrin

doi:10.1016/j.jtemb.2012.03.001

Cited by 17 publications

(8 citation statements)

References 23 publications

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“…Doses of drugs were according to guidelines. Present study result is in accordance with previous study by Donery et al who found that TSH level increased significantly and FT 4 level decreased compared with baseline values and control group 20 . FT 3 level remained unchanged.…”

Section: Resultssupporting

confidence: 93%

Subclinical Hypothyroidism During Valproic Acid Therapy in Children with Epilepsy

Das

Ahmed²,

Chowdhury³

et al. 2019

Chatt Maa Shi Hosp Med Coll J

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Background : Valproic Acid (VPA) is an effective anticonvulsant widely used for the treatment of epilepsy in children, but there are pitfalls in VPA therapy, especially in case of various endocrine organs like thyroid. So the aim of this study was to evaluate the thyroid dysfunction in terms of subclinical hypothyroidism during Valproic Acid (VPA) therapy in children with epilepsy. Methods: The study was conducted in the Department of Paediatrics, and Shishu Bikas Kendra, Chittagong Medical College Hospital (CMCH) over one year duration on 50 newly diagnosed idiopathic epileptic children who were decided to start Valproate at the dose of 20mg/kg/day. At the same time similar number (n=50) of age and sex matched children visited the paediatric OPD for other health events(e.g. acute upper respiratory infection, Influenza like illness and Acute watery diarrhoea) other than epilepsy were included in the study as control group. Thyroid function status like serum levels of Thyroid-Stimulating Hormone (TSH) Free Triiodothyronine (FT3) and Free Thyroxin (FT4) were evaluated at baseline and after six months. Moreover, serum VPA level was also measured in children receiving valproate at follow up visit. Anti thyroid peroxidise antibody (Anti TPO ab) was checked at follow up visit in those having TSH level beyond normal reference range. After collecting all data it was analyzed by SPSS-19. Results: In the current study, cases consisted of 30(60%) male and 20(40%) female children. Male to female ratio was 1.5:1. Gender and age were matched in cases and control group (p>0.05). Most of the population in the cases were from rural areas 29(58%) and most of them 40(80%) belonged to middle class family. The mean±SD of TSH level significantly increased after six months in comparison with base line values (1.76±0.57μIU/ml vs. 2.70±1.50μIU/ml, p<0.05) and with control group at follow up visit (1.74±0.73μIU/ml vs 2.70±1.50μIU, p<0.05). On the other hand, in the control group there were no significant changes of TSH level in comparison with base line (1.82±0.55μIU vs 1.74±0.73μIU/ml, p=0.16). The mean±SD of FT4 value decreased significantly in the cases after six months though remained within normal reference range (1.24±0.27ng/dl vs1.11±0.13ng/dl, p<0.05) FT3 level remained unchanged. Five (10%) epileptic children in the cases were found to have subclinical hypothyroidism at follow up who had TSH level beyond the normal reference range. Anti thyroid peroxidase antibody was negative among them. In contrast, no one in control group was found to have TSH level beyond the normal limit. All cases were clinically euthyroid. No significant correlations were found between TSH level and serum VPA level (r2 = 0.035 p= 0.193). Conclusion: Subclinical hypothyroidism develops in children with epilepsy during VPA therapy. Proper attention should be given so that development of overt hypothyroidism can be avoided. Chatt Maa Shi Hosp Med Coll J; Vol.17 (2); Jul 2018; Page 14-20

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Section: Resultssupporting

confidence: 93%

Subclinical Hypothyroidism During Valproic Acid Therapy in Children with Epilepsy

Das

Ahmed²,

Chowdhury³

et al. 2019

Chatt Maa Shi Hosp Med Coll J

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“…Serum FT4 concentrations in our study were within the normal range, and this is in agreement with some previously published data (Caksen et al ., ; Vainionpaa et al ., ; Verrotti et al ., ). However, other authors reported serum FT4 to be significantly lower in patients receiving VPA treatment despite their clinically euthyroid status (Specchio et al ., ; Castro‐Gago et al ., ; Hirfanoglu et al ., ; Aygun et al ., ; Doneray et al ., ; Turan et al ., ; Yilmaz et al ., ). Although not below the normal range, our patients with elevated TSH levels had lower FT4 serum levels.…”

Section: Discussionmentioning

confidence: 99%

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

Ilić¹,

Bogićević²,

Miljković³

et al. 2016

Epileptic Disorders

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Aim. To identify potential risk factors for the development of subclinical hypothyroidism following long‐term valproic acid monotherapy in children with epilepsy. Methods. Serum levels of thyroid‐stimulating hormone, free thyroxine, free triiodothyronine, thyreoglobulin antibodies, and thyroid peroxidase antibodies were determined in 41 patients and in 41 sex‐ and age‐matched healthy children. Results. Mean valproic acid treatment duration was 2.80±1.96 years. The valproic acid group had higher serum thyroid‐stimulating hormone (p<0.001) and free triiodothyronine (p<0.05) levels compared to the control group. Serum thyroid‐stimulating hormone and free triiodothyronine were above the upper limit for healthy controls in 34% and 32% of patients, respectively, and no clinical features of thyroid dysfunction were observed. Duration of valproic acid monotherapy for less than four years was a risk factor for elevated thyroid‐stimulating hormone levels. Conclusion. One third of children with normal range serum valproic acid levels may have elevated serum thyroid‐stimulating hormone and free triiodothyronine levels, especially in the first four years of treatment.

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“…9,14 A longitudinal, controlled study revealed alterations in serum thyroid profiles were associated with low serum copper. 18 We did not evaluate for mineral deficiencies in our subjects, thus, we cannot comment on these potential effects.…”

Section: Discussionmentioning

confidence: 99%

Valproate use and thyroid dysfunction in children with idiopathic epilepsy

Sibarani¹,

Deliana

Saing

2018

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Background Long-term administration of valproic acid (VPA) has side effects, including thyroid dysfunction. Subclinical hypothyroidism (SCH) identified by elevated serum thyroid stimulating hormone (TSH) concentrations with normal thyroxine (T4) and triiodothyronine (T3), or normal free thyroxine (fT4) and free triiodothyronine (fT3) has been demonstrated in idiopathic epilepsy patients receiving VPA. Objective To evaluate for associations between age at initiation of VPA treatment and duration of treatment with thyroid dysfunction. Methods A cross-sectional study was conducted from October 2012 to May 2013 in Haji Adam Malik and Pirngadi Hospitals, Medan, North Sumatera. Subjects were children ranging from 0 and below 18 years who had been diagnosed with idiopathic epilepsy. Blood specimens were taken to evaluate serum T3, T4, and TSH levels in all subjects. Data were analyzed using bivariate and multivariate analyses. Results A total of 49 subjects were included in the study. Age of ≤ 4 years at initiation of VPA was found to be a significant risk factor for SCH in the bivariate analysis (OR 6.67; 95%CI 1.215 to 36.594, P=0.036). Three factors had P values <0.25 in the bivariate analysis and were subsequently analyzed by stepwise multivariate regression test: age at initiation of VPA, duration of treatment, and drug dosage. The VPA initiation at age <4 years had 6.67 times the risk of SCH than the age of >4 years (95%CI 1.215 to 36.594; P=0.029). Duration of treatment and VPA dosage were not significantly associated with SCH on multivariate analysis Conclusion Age ≤ 4 years old at the initiation of VPA is associated with thyroid dysfunction. However, no significant association was found between duration of treatment as well as drug dosage with thyroid dysfunction.

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Serum thyroid hormone profile and trace elements in children receiving valproic acid therapy: A longitudinal and controlled study

Cited by 17 publications

References 23 publications

Subclinical Hypothyroidism During Valproic Acid Therapy in Children with Epilepsy

Subclinical Hypothyroidism During Valproic Acid Therapy in Children with Epilepsy

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

Valproate use and thyroid dysfunction in children with idiopathic epilepsy

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