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Published on: March 17, 2023
Methimazole-induced hypothyroidism causes cellular damage in the spleen, heart, liver, lung and kidney
Edgar Cano-Europa1, Vanessa Blas-Valdivia, Margarita Franco-Colin
1Departamento de Fisiología "Mauricio Russek Berman", Escuela Nacional de Ciencias Biológicas, I.P.N., Carpio y Plan de Ayala, México, D.F., C.P., Mexico.
Abstract:
It is known that a hypothyroidism-induced hypometabolic state protects against oxidative damage caused by toxins. However, some workers demonstrated that antithyroid drug-induced hypothyroidism can cause cellular damage. Our objective was to determine if methimazole (an antithyroid drug) or hypothyroidism causes cellular damage in the liver, kidney, lung, spleen and heart. Twenty-five male Wistar rats were divided into 5 groups: euthyroid, false thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism (60 mg/kg), and treatment with methimazole (60 mg/kg) and a T₄ injection (20 μg/kg/d sc). At the end of the treatments (4 weeks for the pharmacological groups and 8 weeks for the surgical groups), the animals were anesthetized with sodium pentobarbital and they were transcardially perfused with 10% formaldehyde. The spleen, heart, liver, lung and kidney were removed and were processed for embedding in paraffin wax. Coronal sections were stained with hematoxylin-eosin. At the end of treatment, animals with both the methimazole- and thyroidectomy-induced hypothyroidism had a significant reduction of serum concentration of thyroid hormones. Only methimazole-induced hypothyroidism causes cellular damage in the kidney, lung, liver, heart, kidney and spleen. In addition, animals treated with methimazole and T₄ showed cellular damage in the lung, spleen and renal medulla with lesser damage in the liver, renal cortex and heart. The thyroidectomy only altered the lung structure. The alterations were prevented by T₄ completely in the heart and partially in the kidney cortex. These results indicate that tissue damage found in hypothyroidism is caused by methimazole.
Insights
Methimazole-induced hypothyroidism, not the condition itself, causes cellular damage in rat organs. Thyroid hormone replacement therapy partially or fully reversed these harmful effects.
Area of Science:
- Endocrinology
- Toxicology
- Pathology
Background:
- Hypothyroidism is generally considered protective against oxidative damage.
- However, some studies suggest antithyroid drugs can induce cellular damage.
- The specific role of methimazole versus hypothyroidism in cellular damage remains unclear.
Purpose of the Study:
- To investigate whether methimazole or hypothyroidism causes cellular damage.
- To assess damage in the liver, kidney, lung, spleen, and heart of rats.
Main Methods:
- Wistar rats were divided into five groups: euthyroid, sham thyroidectomy, thyroidectomy-induced hypothyroidism, methimazole-induced hypothyroidism, and methimazole with T₄ treatment.
- Treatments lasted 4-8 weeks.
- Histological analysis of organs (liver, kidney, lung, spleen, heart) using hematoxylin-eosin staining.
Main Results:
- Both methimazole and thyroidectomy induced hypothyroidism, reducing thyroid hormone levels.
- Methimazole-induced hypothyroidism caused significant cellular damage across all assessed organs.
- Thyroidectomy alone primarily altered lung structure.
- T₄ treatment ameliorated damage in the heart and partially in the kidney cortex, but lung, spleen, and renal medulla damage persisted.
Conclusions:
- Cellular damage observed in this study is attributable to methimazole, not hypothyroidism itself.
- Thyroid hormone replacement can mitigate some of the drug-induced tissue damage.
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