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Amiodarone and thyroid hormone action.

J A Franklyn, J R Davis, M D Gammage

    Clinical Endocrinology
    |March 1, 1985
    PubMed
    Summary
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    Amiodarone alters thyroid hormone levels by inhibiting peripheral deiodination and directly affecting the pituitary gland. This drug interferes with thyroid hormone (T3) binding to pituitary cell nuclei, impacting thyroid-stimulating hormone (TSH) release.

    Area of Science:

    • Endocrinology
    • Pharmacology
    • Molecular Biology

    Background:

    • Amiodarone, an antiarrhythmic drug, is known to affect thyroid hormone levels.
    • Clinical observations show altered free thyroxine (T4) and free triiodothyronine (T3) levels in patients on amiodarone therapy.

    Purpose of the Study:

    • To investigate the in vitro effects of amiodarone on thyroid hormone action at the cellular level.
    • To elucidate the direct interaction of amiodarone with thyroid hormone receptors in the anterior pituitary.

    Main Methods:

    • Assessment of serum free T4, free T3, and reverse T3 concentrations in patients on amiodarone.
    • In vitro experiments using isolated rat anterior pituitary cell nuclei to study T3 binding.
    • In vitro studies on cultured rat anterior pituitary cells to measure TSH release.

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    Main Results:

    • Amiodarone therapy increased free T4 and reverse T3, while decreasing free T3, suggesting inhibited peripheral deiodination.
    • In vitro, amiodarone inhibited T3 binding to pituitary cell nuclei in a dose-dependent manner.
    • Amiodarone stimulated TSH release from cultured pituitary cells, indicating a T3 antagonistic effect.

    Conclusions:

    • Amiodarone directly influences the anterior pituitary thyrotroph cells.
    • The drug's action is mediated through interference with nuclear T3 receptor binding.
    • These findings explain the altered thyroid-stimulating hormone levels observed in patients treated with amiodarone.