EFFECT OF ANTIEPILEPTIC DRUG THERAPY ON THYROID FUNCTION AND THYROID VOLUME IN CHILDREN WITH SEIZURE DISORDERS: A PROSPECTIVE OBSERVATIONAL STUDY
DOI:
https://doi.org/10.22159/ajpcr.2026v19i4.58458Keywords:
Antiepileptic drugs, Thyroid function, Thyroid volume, Pediatric epilepsy, Adverse drug reactions, EpilepsyAbstract
Objectives: The objective of the study is to evaluate the effect of antiepileptic drug (AED) therapy on thyroid function parameters and thyroid volume in children aged 2–12 years with seizure disorders.
Methods: This prospective observational study included 45 children aged 2–12 years with seizure disorders receiving antiepileptic therapy and followed for 6 months. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid volume by ultrasonography were assessed at baseline, 3 months, and 6 months. Participants received monotherapy or polytherapy, predominantly sodium valproate, phenytoin, and levetiracetam. Data were analyzed using repeated measures analysis of variance and the Mann–Whitney U test (p<0.05 considered significant).
Results: The mean age of participants was 7.29±2.69 years. On pooled analysis, mean TSH levels showed a mild, non-significant increase over time (p=0.40), while FT3 and FT4 levels remained stable. However, children receiving sodium valproate demonstrated a statistically significant rise in mean TSH from 3.07±1.45 to 3.24±1.56 mIU/L at 6 months (p=0.032), with normal FT3 and FT4 levels. Subgroup analysis confirmed that this significant change was observed only with sodium valproate (p=0.032). Thyroid volume showed a marginal, non-significant increase during follow-up (p=0.15), with no significant difference between monotherapy and polytherapy groups.
Conclusion: Sodium valproate therapy in children is associated with a significant rise in TSH levels suggestive of subclinical hypothyroidism. Periodic thyroid function monitoring every 6–12 months is advisable in children receiving long-term sodium valproate therapy.
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References
1. Wallace H, Shorvon S, Tallis R. Age-specific incidence and prevalence rates of treated epilepsy in an unselected population of 2,052,922 and age-specific fertility rates of women with epilepsy. Lancet. 1998;352(9145):1970-3. doi: 10.1016/S0140-6736(98)04512-7, PMID 9872246
2. Behrman RE, Kliegman RM, Jenson HB. Nelson Textbook of Pediatrics. 16th ed. Philadelphia, PA: W B Saunders; 2000. p. 1813-32.
3. Isojärvi JI, Pakarinen AJ, Myllylä VV. Thyroid function in epileptic patients treated with carbamazepine. Arch Neurol. 1989;46(11):1175-8. doi: 10.1001/archneur.1989.00520470029021, PMID 2510703
4. Verrotti A, Greco R, Latini G, Chiarelli F. Endocrine and metabolic changes in epileptic patients receiving valproic acid. J Pediatr Endocrinol Metab. 2005;18(5):423-30. doi: 10.1515/jpem.2005.18.5.423, PMID 15921170
5. Oppenheimer JH. Thyroid hormone action at the cellular level. Science. 1979;203(4384):971-9. doi: 10.1126/science.218285, PMID 218285
6. Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: Clinical observations and experimental findings. J Neuroendocrinol. 2004;16(10):809-18. doi: 10.1111/j.1365- 2826.2004.01243.x, PMID 15500540
7. Monzani F, Del Guerra P, Caraccio N, Pruneti CA, Pucci E, Luisi M, et al. Subclinical hypothyroidism: Neurobehavioral features and beneficial effect of L-thyroxine treatment. Clin Investig. 1993;71(5):367-71. doi: 10.1007/BF00186625, PMID 8508006
8. Liewendahl K, Majuri H, Helenius T. Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs. Clin Endocrinol (Oxf). 1978;8(3):185-91. doi: 10.1111/j.1365-2265.1978. tb01493.x, PMID 346267
9. Strandjord RE, Aanderud S, Myking OL, Johannessen SI. Influence of carbamazepine on serum thyroxine and triiodothyronine in patients with epilepsy. Acta Neurol Scand. 1981;63(2):111-21. doi: 10.1111/ j.1600-0404.1981.tb00754.x, PMID 6782820
10. Oppenheimer JH, Fisher LV, Nelson KM, Jailer JW. Depression of the serum protein-bound iodine level by diphenylhydantion. J Clin Endocrinol Metab. 1961;21:252-62. doi: 10.1210/jcem-21-3-252, PMID 13731058
11. 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):426-30. doi: 10.1016/j.pediatrneurol.2007.07.003, PMID 18021925
12. Kim SH, Chung HR, Kim SH, Kim H, Lim BC, Chae JH, et al. Subclinical hypothyroidism during valproic acid therapy in children and adolescents with epilepsy. Neuropediatrics. 2012;43(3):135-9. doi: 10.1055/s-0032-1313913, PMID 22618302
13. Elshorbagy HH, Barseem NF, Suliman HA, Talaat E, Alshokary AH, Abdelghani WE, et al. The impact of antiepileptic drugs on thyroid function in children with epilepsy: New versus old. Iran J Child Neurol. 2020;14(1):31-41. PMID 32021626
14. Aanderud S, Myking OL, Strandjord RE. The influence of carbamazepine on thyroid hormones and thyroxine binding globulin in hypothyroid patients substituted with thyroxine. Clin Endocrinol (Oxf). 1981;15(3):247-52. doi: 10.1111/j.1365-2265.1981.tb00662.x, PMID 6796303
15. Brunn J, Block U, Ruf G, Bos I, Kunze WP, Scriba PC. Volumetrie der schilddrüsenlappenmittels real-time-sonographie [volumetric analysis of thyroid lobes by real-time ultrasound (author’s transl)]. Dtsch Med Wochenschr. 1981;106(41):1338-40. doi: 10.1055/s-2008-1070506, PMID 7274082
16. WHO, ICCIDD. Recommended normative values for thyroid volume in children aged 6-15 years. World Health Organization & international council for control of iodine deficiency disorders. Bull World Health Organ. 1997;75(2):95-7. PMID 9185360
17. Das M, Sehgal VK, Singh H. Adverse drug reactions of anti-epileptic drugs in pediatric age group in a tertiary care teaching hospital; A cross-sectional study. Asian J Pharm Clin Res. 2022;15(3):4-7. doi: 10.22159/ ajpcr.2022v15i3.43425
18. Kaur P, Kaur A, Singh J, Singh H. Prescription pattern of antiepileptic drugs in children with epilepsy: A cross-sectional study. Asian J Pharm Clin Res. 2023;16(5):99-103. doi: 10.22159/ajpcr.2023.v16i5.47126
19. Agarwal P, Bakshi V. Development of gabapentin-loaded solid lipid nanoparticle for alleviating seizure activity in picrotoxin and bicuculline-induced rats. Int J Appl Pharm. 2024;16(6):224-37. doi: 10.22159/ijap.2024v16i6.51157
20. Meilani, Ichsan B. Potential problems in generic substitution of antiepileptic drugs: Systematic review. Int J Appl Pharm. 2025;17(2):13-20.
21. Baravkar AA, Shinde SD, Aher NB. Role of biomarkers in epileptogenesis: A concise review. Int J Pharm Pharm Sci. 2022;14(1):9- 12. doi: 10.22159/ijpps.2022v14i1.43306
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