Thyroid Function in Children With Epilepsy Treated With Sodium Valproate Monotherapy

Attilakos, Achilleas; Katsarou, Eustathia; Prassouli, Alexia; Mastroyianni, Sotiria; Voudris, Konstantinos; Fotinou, Aspasia; Garoufi, Anastasia

doi:10.1097/wnf.0b013e318166cbcd

Cited by 22 publications

(18 citation statements)

References 11 publications

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“…Our results show that duration of VPA treatment for less than four years may be a risk factor for elevated TSH levels. Moreover, increase in serum TSH during the first year of VPA treatment (Cansu et al ., ; Attilakos et al ., ; Aygun et al ., ; Kafadar et al ., ), and/or during the first 24 or 36 months of therapy (Tanaka et al ., ; Sahu et al ., ), has been reported, in accordance with our results. Nevertheless, some authors reported no effect of length of treatment on TSH levels (Aggarwal et al ., ; Kim et al ., ), but their patients were administered VPA during a shorter period compared to our study.…”

Section: Discussionmentioning

confidence: 98%

“…Decreased levels of free thyroxine (FT4) and free triiodothyronine (FT3) with unchanged or elevated levels of thyroid stimulating hormone (TSH) were shown in several studies with carbamazepine, oxcarbazepine and phenobarbital (Cansu et al, 2006;Hirfanoglu et al, 2007;Verrotti et al, 2009;Aggarwal et al, 2011;Turan et al, 2014;Kafadar et al, 2015), but the association between the use of valproic acid (VPA) and thyroid dysfunction remains controversial. Some studies showed that VPA leads to subclinical hypothyroidism with TSH levels in the range of 5-25 mIU/l or significantly higher than those of the control group, and unchanged or decreased levels of FT3 and FT4 (Vainionpaa et al, 2004;Cansu et al, 2006;Castro-Gago et al, 2007;Hirfanoglu et al, 2007;Mikati et al, 2007;Attilakos et al, 2009;Aggarwal et al, 2011;Aygun et al, 2012), while others reported no significant change in the homeostasis of thyroid hormones (Specchio et al, 1985;Tanaka et al, 1987;Verrotti et al, 2001;Caksen et al, 2002;Verrotti et al, 2009). Moreover, there seems to be even more controversy regarding risk factors for thyroid dysfunction, such as age, duration of VPA treatment, daily dosage, and serum level of the drug.…”

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confidence: 99%

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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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Section: Discussionmentioning

confidence: 98%

mentioning

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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“…In several studies, TSH elevations in valproate-treated patients with epilepsy were observed. 13,[18][19][20] However, others have not detected significant alterations of thyroid indices in subjects on valproate treatment. 14,16,21 Our findings are in agreement with the latter studies as we did not observe significantly increased TSH levels in subjects on valproate treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Inconsistent findings have been reported on the effects of valproate on thyroid parameters. In several studies, TSH elevations in valproate‐treated patients with epilepsy were observed 13,18–20 . However, others have not detected significant alterations of thyroid indices in subjects on valproate treatment 14,16,21 .…”

Section: Discussionmentioning

confidence: 99%

Thyroid status in a large cohort of patients with mental retardation: the TOP-R (Thyroid Origin of Psychomotor Retardation) study

Visser

Rijke

Toor

et al. 2011

Clinical Endocrinology

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“…None of these studies reported overt manifestations of thyroid abnormalities. Reduction in fT4 and increase in TSH levels were reported as early as one to three months after starting treatment with CBZ, PB or VPA (20,25). Also, previous studies demonstrated that the changes induced by these drugs are transient (4,16).…”

Section: Introductionmentioning

confidence: 96%

Thyroid Gland Volume in Adults with Epilepsy: Relationship to Thyroid hormonal function

Hamed

Radwan²,

Elaal³

et al. 2015

neurol neurosci

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Several studies were done investigating thyroid function in patients with epilepsy. However the results of different studies were conflicting or controversial. This study aimed to evaluate thyroid hormonal changes and their relationship to thyroid volume in epileptic adults on long-term treatment with antiepileptic drugs (AEDs). This study included 135 adults with idiopathic epilepsy with mean age of 32.32±4.34years, duration of illness of 10.52±5.08 years and on treatment with carbamazepine (CBZ), valproate (VPA) or CBZ+VPA for a mean duration of 8.66±3.32years. The serum levels of free thyroxine (fT4), triiodothyronine (fT3), and thyroid-stimulating hormone (TSH) were assessed. Thyroid volume was measured using ultrasonography. Compared to control subjects, patients had significant lower fT4 (p<0.01) and fT3 (p<0.01) and higher levels of TSH (p<0.0001). The majority of patients with reduced fT4 also had reduced fT3 and increased TSH levels. Nearly 26% of the patients had enlargement of the thyroid gland (p<0.001). Patients on polytherapy had more thyroid volume compared to patients on monotherapy (p<0.05) and patients on VPA had more thyroid volume compared to patients on CBZ (p<0.03). All patients were clinically euthyroid. Significant correlations were identified between fT4 concentrations and duration of illness, dose, serum level and duration of AEDs treatment, fT3 and TSH concentrations and between thyroid volume and fT4, fT3 and TSH concentrations. In conclusion, CBZ and VPA as mono-or polytherapies may cause thyroid hormonal and structural abnormalities. Thyroid enlargement is due to associated subclinical hypothyroidsm. This data have implications suggesting prevention strategies.

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Thyroid Function in Children With Epilepsy Treated With Sodium Valproate Monotherapy

Cited by 22 publications

References 11 publications

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

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

Thyroid status in a large cohort of patients with mental retardation: the TOP-R (Thyroid Origin of Psychomotor Retardation) study

Thyroid Gland Volume in Adults with Epilepsy: Relationship to Thyroid hormonal function

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