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Effect of antiepileptic drugs on the thyroid gland in adult albino rats: hormonal assay, histological and morphometric study

El-Bermawy, Manal I.

The Egyptian Journal of Histology: March 2015 - Volume 38 - Issue 1 - p 10–20
doi: 10.1097/01.EHX.0000459779.85453.da
Original articles

Background Normal thyroid hormone blood levels are essential for the growth and development of tissues and maintenance of organ function. Antiepileptic drugs may induce disturbances in thyroid hormonal levels.

Aim This study was conducted to evaluate the effects of antiepileptic drugs on the thyroid gland of adult male albino rats using hormonal assay, histological study, and morphometric study.

Materials and methods This study included 30 adult male albino rats divided into control and experimental groups. The latter group was equally subdivided into two subgroups (IIA and IIB). Rats of subgroups IIA and IIB were given 200 mg/kg/day valproate sodium and100 mg/kg/day phenytoin, respectively, for 5 weeks through a gastric tube. After 5 weeks, blood samples of all rats were taken for hormonal assay. Thereafter, all rats were sacrificed and specimens of thyroid glands were extracted and processed for histological and morphometric studies.

Results In subgroup IIA (valproate-treated group), hormonal assay revealed mild significant decrease in serum T3 and T4, with decrease in free thyroxine (FT4) and increased thyroid stimulating hormone. Mild thyroid follicle changes were observed with mild interstitial exudate and amalgamated highly stained colloid in some follicular lumen. Morphometric study showed increased follicular epithelial height and decreased dimensions of follicles. However, in subgroup IIB (phenytoin-treated group), hormonal assay showed moderate significant decrease in serum T3 and T4, with decreased FT4 and nonsignificant changes in thyroid stimulating hormone levels. It also revealed signs of thyroid follicle destruction as disrupted follicles with desquamated follicular cells in their lumen and severe interstitial exudate. Highly vacuolated cytoplasm in the follicular cells and amalgamated scanty colloid in the follicular lumen were seen. Morphometric study demonstrated decreased follicular epithelial height and dimensions of follicles.

Conclusion Study clarified less damaging effects of valproate sodium compared with phenytoin on the thyroid gland and its hormones. Therefore, the use of these drugs should be justified in clinical situations under direct medical supervision.

Anatomy Department, Faculty of Medicine, Tanta University, Tanta, Egypt

Correspondence to Manal I. El-Bermawy, MD, Anatomy Department, Faculty of Medicine, Tanta University, Tanta, Egypt Tel: +20 100 124 8580; fax: +0403332033; e-mail:

Received July 5, 2014

Accepted December 12, 2014

© 2015 The Egyptian Journal of Histology
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