Brief Communication: NO EFFECT OF LONG-TERM VALPROATE THERAPY ON THYROID AND PARATHYROID FUNCTIONS IN CHILDREN

Çaksen, Hüseyîn; Dülger, Haluk; Cesur, Yaşar; Odabaş, Dursun; Tuncer, Oğuz; Ataş, Bülent

doi:10.1080/00207450290158269

Cited by 20 publications

(25 citation statements)

References 8 publications

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“…According to some authors, serum FT3 during VPA treatment can remain unchanged (Caksen et al ., ; Verrotti et al ., ; Aggarwal et al ., ; Aygun et al ., ) or decrease (Eiris‐Punal et al ., ). Our study demonstrated significantly higher serum FT3 in the VPA group, compared to healthy controls.…”

Section: Discussionmentioning

confidence: 98%

“…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 ., ).…”

Section: Discussionmentioning

confidence: 99%

“…The primary treatment option is the use of antiepileptic drugs (AEDs) and patients often require long-term and sometimes life-long treatment (Freitag et al, 2001). However, the use of AEDs has been associated with thyroid disorders, in particular subclinical hypothyroidism, in paediatric patients (Caksen et al, 2002;Castro-Gago et al, 2007;Hirfanoglu et al, 2007). This is a major concern for clinicians since it has been demonstrated that even minor changes in thyroid metabolism during childhood may cause growth and developmental disorders, as V. Ilić, et al well as cognitive impairment and subtle neuromuscular abnormalities (Monzani et al, 1993;Jensovsky et al, 2002;Setian, 2007).…”

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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%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…At least one study has found that children administered VPA for epilepsy showed evidence of hypothyroidism [179], while another study suggested that VPA was associated with increases in thyroid stimulating hormone [116]. However, these findings have not been replicated [180] and do not provide substantial evidence that VPA clinically affects thyroid function. Nonetheless, thyroid function remains an important point of clinical care for women with bipolar disorder, as it has a higher rate of dysfunction in this population and is associated with lithium use.…”

Section: Estrogen Progesterone and Thyroid Hormonesmentioning

confidence: 97%

Valproate and Neuroendocrine Changes in Relation to Women Treated for Epilepsy and Bipolar Disorder: A Review

Reynolds¹,

Sisk²,

Rasgon³

2007

CMC

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Valproic acid (2-n-propylpentanoic acid, VPA) is well-established as a mood-stabilizer for bipolar disorder, in addition to its application as a treatment in neurological disorders such as epilepsy, migraine headaches, and chronic neuropathic pain. Its mechanisms of actions in any of the disorders have not yet been fully elucidated but currently include GABA-ergic inhibitory effects, the suppression of NMDA-mediated excitatory neurotransmission, and possibly effects on monoamines and cerebral glucose metabolism. Given the rising use of VPA by women of reproductive age for various conditions it is increasingly important to understand how VPA affects reproductive and metabolic function in women, yet a number of key issues regarding VPA use in women of reproductive age remain unclear. These include the question of whether VPA use is associated with the development of polycystic ovary syndrome (PCOS)-like features (such as elevated androgen concentrations and/or chronic anovulation). The metabolic effects of VPA use, particularly on insulin sensitivity and weight gain, are also important to understand. Lastly, questions of VPA use during pregnancy and lactation require continued attention. This article reviews the current understanding of VPA's mechanisms of action, effects on the reproductive and metabolic system, and teratogenic qualities, highlighting important future areas of study.

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“…A recent systematic review of the untoward effects of valproate showed that drug-induced parkinsonism is a relatively common side effect in elderly women 6 . It's known that valproate can safely be used in patients with thyroid and parathyroid dysfunction, once it does not interfere on these hormone levels 7 . The mechanism of how valproate can induce trismus is unclear.…”

Section: Dear Editormentioning

confidence: 99%

Trismus secondary to valproate treatment in a woman with bipolar disorder: a case report

Bermudez

Gracia

Garcia

et al. 2017

Arch. Clin. Psychiatry (São Paulo)

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Muscle contracture is a common symptom of valproate. However, there is no report in the literature of lockjaw (trismus) associated with this drug. We therefore present a case of lockjaw during valproate treatment in a patient with bipolar disorder and hypoparathyroidism.A 62-year-old Caucasian female was admitted on November, 2015 at a psychiatric unit during a manic episode. Patient was previously diagnosed with bipolar disorder and had manic and depressive episodes in the past. She underwent a total thyroidectomy three months prior to her admission, for suspicion of malignancy (not confirmed by biopsy) and has been since then in treatment for hypothyroidism and iatrogenic hypoparathyroidism with levothyroxine, calcitriol and calcium carbonate. She had no cognitive impairment and no relevant findings in laboratory exams. A cerebral perfusion scintigraphy was performed showing slight hypoperfusion in the frontal lobe and posterior cerebellar areas. It is noteworthy that the patient did not tolerate lithium carbonate due to severe extremity tremors. Therefore, valproate was initiated and gradually increased up to 1000 mg/day. She developed lockjaw three days after. She was unable to open her mouth and also fractured two teeth. She had difficulty in diction and in chewing food. No painful symptom or other muscular manifestation had been reported. Biperiden and clonazepam were prescribed without response. She had no prior symptoms of muscular spasm and she denied previous use of valproate. The diagnosis of valproate-induced trismus was made after other causes of trismus, such as infections, neurological illness and oro-dental abnormalities were excluded. The laboratory tests show no alterations on serum levels of TSH, PTH, phosphate and calcium. Thus, the valproate was replaced by olanzapine, which lead to symptom resolution. Patient has been in follow-up for two years and did not have any trismus symptoms since valproic acid withdrawal.Trismus is defined as a tonic contraction of the muscles of mastication with mouth opening of ≤ 35 mm 1 . It can result in difficulty in activities such as biting, chewing, swallowing and speaking and may further lead to poor oral hygiene, pain and weight loss 2 . Some of the causal factors implicated in this condition are tumors, infections, surgery and radiotherapy complications, and drugs side effect 3 . There are case reports of trismus induced by succinylcholine 4 and duloxetine 5 , but none regarding this side effect with valproate. A recent systematic review of the untoward effects of valproate showed that drug-induced parkinsonism is a relatively common side effect in elderly women 6 . It's known that valproate can safely be used in patients with thyroid and parathyroid dysfunction, once it does not interfere on these hormone levels 7 . The mechanism of how valproate can induce trismus is unclear. A preclinical study found that low concentrations of valproate can induce muscle contractions, which were abolished by indomethacin.8 Therefore, prostaglandins may be implicated in...

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Brief Communication: NO EFFECT OF LONG-TERM VALPROATE THERAPY ON THYROID AND PARATHYROID FUNCTIONS IN CHILDREN

Cited by 20 publications

References 8 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

Valproate and Neuroendocrine Changes in Relation to Women Treated for Epilepsy and Bipolar Disorder: A Review

Trismus secondary to valproate treatment in a woman with bipolar disorder: a case report

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