Subclinical Hypothyroidism during Valproic Acid Therapy in Children and Adolescents with Epilepsy

Kim, Se Hee; Chung, Hye Rim; Kim, Seung Hyo; Kim, Hunmin; Lim, Byung Chan; Chae, Jong Hee; Kim, Ki Joong; Hwang, Yong Seung

doi:10.1055/s-0032-1313913

Cited by 33 publications

(51 citation statements)

References 22 publications

(32 reference statements)

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“…We include this description of these subjects to avoid the lost to follow-up because of sudden death [22] and the diagnostic bias due to other exposure status. Specifically, patients with known autoimmune diseases [23] or using drugs that may interfere with thyroid function [24,25] are prone to develop autoimmune thyroiditis or subclinical hypothyroidism. Furthermore, 2 subjects refused to continue the study and 3 were lost to follow-up.…”

Section: Methodsmentioning

confidence: 99%

Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

et al. 2014

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Background/Aims: The natural history of thyroid function in children with Down's syndrome is relatively unknown. We hypothesized that in these patients the occurrence of thyroid dysfunction rises during development. Methods: Thyroid function was assessed yearly in 145 children with Down's syndrome, all followed from birth up to 10 years of age. Heteroskedastic binary and ordinary logistic regression for repeated measures was used to evaluate the relationship of thyroid function with continuous time. Results: Congenital hypothyroidism was detected in 7% of cases. The probability of acquired thyroid dysfunction increased from 30% at birth to 49% at 10 years (p < 0.001). The subclinical hypothyroidism was nearly stable during the follow-up. The probability of hypothyroidism increased from 7 to 24% at 10 years (p < 0.001). Positive anti-thyroglobulin antibodies were associated with higher odds of more severe hypothyroidism (odds ratio 3.6). Positive anti-thyroid peroxidase antibodies were a better predictor of more severe hypothyroidism (odds ratio 6.1). Diffuse hypoechogenicity on thyroid ultrasound was found in 34 out of 145 children. Conclusion: The probability of thyroid dysfunction increasing during development is higher than previously reported. Such children should be carefully monitored annually to early identify thyroid dysfunction.

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Section: Methodsmentioning

confidence: 99%

Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

et al. 2014

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“…Some studies showed an association of age and/or duration of VPA treatment with thyroid hormone imbalance (Mikati et al ., ; Sahu et al ., ), while others have reported opposing results (Tanaka et al ., ; Castro‐Gago et al ., ; Hirfanoglu et al ., ). In addition, significant correlations between the levels of thyroid hormones and VPA daily dosage or serum concentration have been reported (Kim et al ., ).…”

mentioning

confidence: 97%

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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“…Isojarvi et al (8) reported reduced levels of fT4 in 50-100% of patients on CBZ-VPA. Previous studies reported that polytherapy was associated with SCH (19,23). The altered thyroid function during CBZ medication and been attributed to induction of the hepatic P-450 enzyme system and the consequent increase in the metabolism of thyroid hormones (3)(4)(5)(6)11,37).…”

Section: Discussionmentioning

confidence: 99%

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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Subclinical Hypothyroidism during Valproic Acid Therapy in Children and Adolescents with Epilepsy

Cited by 33 publications

References 22 publications

Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

Ten-Year Longitudinal Study of Thyroid Function in Children with Down's Syndrome

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

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

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