Valproate-associated weight gain: Potential relation to energy expenditure and metabolism in patients with epilepsy

Gidal, Barry E.; Anderson, Gail D.; Spencer, Nancy W.; Maly, Melissa M.; Murty, Jessica Vedhamani Murty A P David J; Pitterle, Michael E.; Collins, Douglas; Davis, Lisa

doi:10.1016/s0896-6974(96)00041-2

Cited by 28 publications

(17 citation statements)

References 26 publications

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“…Because the TRH-stimulated TSH responses were unaltered by these drugs, we are against this hypothesis. Blank and Joffe (33,45) suggested that CBZ may alter thyroid hormone levels affecting directly TSH or TRH, but our data do not support this possibility. In agreement with other authors (5,19,26), TSH levels do not increase in CBZ-treated patients, the cause is not activated by the positive feedback mechanism, which should result from low serum thyroid hormone concentrations and serum thyroid hormone levels remain low.…”

Section: Discussioncontrasting

confidence: 90%

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Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

Verrotti

Laus

Sereno

et al. 2009

European Journal of Endocrinology

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Objective: This study evaluates the effects of long-term carbamazepine (CBZ) and valproate acid (VPA) therapy on thyroid function in epileptic children. Design: A prospective study performed in 32 newly diagnosed pediatric patients, subdivided into two groups: 18 patients treated with CBZ and 14 patients treated with VPA. Thirty-two sex-and agematched subjects served as controls. Methods: Serum TSH, thyroxine (T 4 ), triiodothyronine (T 3 ), free thyroxine (fT 4 ), free triiodothyronine (fT 3 ), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (TG-Ab) were evaluated at baseline and at the 3rd, 6th, and 12th month in all patients and in the control group. A TRH stimulation test was performed in all epileptic patients at baseline and at the 3rd, 6th, and 12th month evaluations while in controls only baseline assessment was carried out. Results: At baseline evaluation, thyroid function was normal in all epileptic children. After 3 months, CBZ-treated patients showed serum T 4 and fT 4 levels significantly lower than baseline evaluation and control subjects. Serum T 4 and fT 4 concentrations were unaffected by VPA monotherapy. Serum T 3 and fT 3 were normal in both CBZ-treated and VPA-treated patients. TRH test was normal in all patients. At 6th and 12th month evaluations, the same alterations were present in CBZ-treated patients while thyroid function remained normal in VPA-treated patients. TRH test responses were normal in all epileptic patients. TPO-Ab and TG-Ab were always absent in all patients. Conclusions: Our data suggest that VPA monotherapy does not alter thyroid hormones. On the contrary, alterations of thyroid hormones occur in CBZ-treated children. However, the patients are euthyroid and thyroid hormone alterations are not associated with clinical or subclinical hypothyroidism.

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Section: Discussioncontrasting

confidence: 90%

“…The clinical significance of this increase is uncertain but seems to be a compensatory response in at least some of the patients. No association was also found between serum thyroid hormone concentrations and VPA related obesity (30,33).…”

Section: Discussionmentioning

confidence: 88%

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

Verrotti

Laus

Sereno

et al. 2009

European Journal of Endocrinology

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“…29 VPA-related weight gain has been similar in both sexes in previous studies. 18,[29][30][31] Although obese men taking VPA for epilepsy show an increase in insulin resistance with hyperinsulinemia similar to that seen in obese women on VPA, their serum triglyceride levels are not as high, nor are their HDL-cholesterol/ total cholesterol ratios as low as the women's. Therefore, even though 35% of the men taking VPA are hyperinsulinemic, the condition seems to be milder than that in obese VPA-treated women with epilepsy.…”

Section: Discussionmentioning

confidence: 93%

Fasting serum insulin and lipid levels in men with epilepsy

Pylvänen

Knip²,

Pakarinen³

et al. 2003

Neurology

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“…Gidal et al 15 proposed that the hyperinsulinemic effect of VPA may be due to obesity. Obesity lowers tissue response to insulin, leading to hyperinsulinemia 16 .…”

Section: Discussionmentioning

confidence: 99%

Valproate-induced Insulin Resistance in Prepubertal Girls with Epilepsy

Tan

Orbak²,

Kantarcı³

et al. 2005

Journal of Pediatric Endocrinology and Metabolism

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Valproate is commonly used for treatment of a variety of seizure types in both children and adults. However, if the medication is started before the age of 20 years, it may affect reproductive endocrine functions. In order to investigate the possible role of valproate treatment in the development of obesity, hyperinsulinism and polycystic ovaries, we studied metabolic parameters and ovarian morphology/ size in prepubertal girls with epilepsy. Our study included 14 girls with epilepsy and 15 healthy age-matched controls. The age of the patients ranged from 7 years to 13 years. Mean body weight, fasting serum insulin and glucose levels and HOMA index of girls in the study group were significantly greater than those of the control girls (p <0.05). Serum androstenedione, prolactin and free testosterone were significantly lower in the VPA-treated girls than in the controls, whereas SHBG level was higher (p <0.05). There was no difference between the groups for ovarian morphology. In conclusion, our findings showed that valproate treatment may lead to hyperinsulinemia and hypoandrogenism during the prepubertal period. This emphasizes that a mature adult endocrine system may not be necessary for the development of VPA-related hyperinsulinemia.

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Valproate-associated weight gain: Potential relation to energy expenditure and metabolism in patients with epilepsy

Cited by 28 publications

References 26 publications

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

Fasting serum insulin and lipid levels in men with epilepsy

Valproate-induced Insulin Resistance in Prepubertal Girls with Epilepsy

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