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

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

doi:10.1055/s-0032-1313913

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2012; 43(03): 135-139
DOI: 10.1055/s-0032-1313913

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

Autor*innen

Se Hee Kim

¹Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University, College of Medicine, Seoul, Republic of Korea
Hye Rim Chung

²Department of Pediatrics, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea
Seung Hyo Kim

³Department of Pediatrics, Cheju National University, College of Medicine, Cheju, Republic of Korea
Hunmin Kim

²Department of Pediatrics, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea
Byung Chan Lim

¹Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University, College of Medicine, Seoul, Republic of Korea
Jong Hee Chae

¹Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University, College of Medicine, Seoul, Republic of Korea
Ki Joong Kim

¹Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University, College of Medicine, Seoul, Republic of Korea
Yong Seung Hwang

¹Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University, College of Medicine, Seoul, Republic of Korea
Hee Hwang

²Department of Pediatrics, Seoul National University, Bundang Hospital, Seongnam, Republic of Korea

Abstract

The aim of this study was to evaluate the incidence of thyroid dysfunction during valproic acid (VPA) therapy in children and adolescents with epilepsy. The serum levels of thyroid-stimulating hormone (TSH), free thyroxine, and triiodothyronine were evaluated in 61 children with epilepsy who received VPA monotherapy for more than 6 months and in 144 controls. We analyzed the effect of age, seizure type, duration of VPA treatment, dose of VPA, and serum level of VPA on thyroid function. The incidence of subclinical hypothyroidism was significantly higher in patients with VPA therapy than in controls (52.4 vs. 16.7%; p < 0.001). In addition, of the 61 patients, 5 (8.1%) exhibited TSH levels that were >10 μIU/mL. However, none of the patients and controls showed overt hypothyroidism. Serum VPA level and daily dose of VPA were correlated with TSH level. Subclinical hypothyroidism developed frequently in children and adolescents during VPA therapy.

Keywords

hypothyroidism - valproic acid - epilepsy - anticonvulsant - children

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Referenzen

References
1 Abaci A, Saygi M, Yis U, Demir K, Dirik E, Bober E. Metabolic alterations during valproic acid treatment: a prospective study. Pediatr Neurol 2009; 41 (6) 435-439
2 Çaksen H, Dülger H, Cesur Y, Odabaş D, Tuncer O, Ataş B. No effect of long-term valproate therapy on thyroid and parathyroid functions in children. Int J Neurosci 2002; 112 (11) 1371-1374
3 Hirfanoglu T, Serdaroglu A, Camurdan O , et al. Thyroid function and volume in epileptic children using carbamazepine, oxcarbazepine and valproate. Pediatr Int 2007; 49 (6) 822-826
4 Isojärvi JIT, Pakarinen AJ, Myllylä VV. Thyroid function with antiepileptic drugs. Epilepsia 1992; 33 (1) 142-148
5 Verrotti A, Basciani F, Morresi S, Morgese G, Chiarelli F. Thyroid hormones in epileptic children receiving carbamazepine and valproic acid. Pediatr Neurol 2001; 25 (1) 43-46
6 Verrotti A, Laus M, Scardapane A, Franzoni E, Chiarelli F. Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate. Eur J Endocrinol 2009; 160 (1) 81-86
7 Attilakos A, Katsarou E, Prassouli A , et al. Thyroid function in children with epilepsy treated with sodium valproate monotherapy: a prospective study. Clin Neuropharmacol 2009; 32 (1) 32-34
8 Cansu A, Serdaroğlu A, Çamurdan O, Hirfanoğlu T, Bideci A, Gücüyener K. The evaluation of thyroid functions, thyroid antibodies, and thyroid volumes in children with epilepsy during short-term administration of oxcarbazepine and valproate. Epilepsia 2006; 47 (11) 1855-1859
9 Castro-Gago M, Novo-Rodríguez MI, Gómez-Lado C, Rodríguez-García J, Rodríguez-Segade S, Eirís-Puñal J. Evolution of subclinical hypothyroidism in children treated with antiepileptic drugs. Pediatr Neurol 2007; 37 (6) 426-430
10 Eirís-Puñal J, Del Río-Garma M, Del Río-Garma MC, Lojo-Rocamonde S, Novo-Rodríguez I, Castro-Gago M. Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism. Epilepsia 1999; 40 (12) 1761-1766
11 Mikati MA, Tarabay H, Khalil A, Rahi AC, El Banna D, Najjar S. Risk factors for development of subclinical hypothyroidism during valproic acid therapy. J Pediatr 2007; 151 (2) 178-181
12 Vainionpää LK, Mikkonen K, Rättyä J , et al. Thyroid function in girls with epilepsy with carbamazepine, oxcarbazepine, or valproate monotherapy and after withdrawal of medication. Epilepsia 2004; 45 (3) 197-203
13 Berg AT, Berkovic SF, Brodie MJ , et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia 2010; 51 (4) 676-685
14 Biondi B, Cooper DS. The clinical significance of subclinical thyroid dysfunction. Endocr Rev 2008; 29 (1) 76-131
15 Jung CH, Sung KC, Shin HS , et al. Thyroid dysfunction and their relation to cardiovascular risk factors such as lipid profile, hsCRP, and waist hip ratio in Korea. Korean J Intern Med 2003; 18: 146-153
16 Löscher W, Schmidt D. Increase of human plasma GABA by sodium valproate. Epilepsia 1980; 21 (6) 611-615
17 Graf WD, Oleinik OE, Glauser TA, Maertens P, Eder DN, Pippenger CE. Altered antioxidant enzyme activities in children with a serious adverse experience related to valproic acid therapy. Neuropediatrics 1998; 29 (4) 195-201
18 Surks MI, Sievert R. Drugs and thyroid function. N Engl J Med 1995; 333 (25) 1688-1694
19 Gharib H, Tuttle RM, Baskin HJ, Fish LH, Singer PA, McDermott MT. Subclinical thyroid dysfunction: a joint statement on management from the American Association of Clinical Endocrinologists, the American Thyroid Association, and the Endocrine Society. J Clin Endocrinol Metab 2005; 90 (1) 581-585 , discussion 586–587
20 Jones DD, May KE, Geraci SA. Subclinical thyroid disease. Am J Med 2010; 123 (6) 502-504
21 Surks MI, Ortiz E, Daniels GH , et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291 (2) 228-238