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Phenytoin and thyroid hormone action.

J A Franklyn, J R Davis, D B Ramsden

    The Journal of Endocrinology
    |February 1, 1985
    PubMed
    Summary
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    Phenytoin reduces thyroid hormone (T3) binding in pituitary cell nuclei, suggesting it directly impacts thyroid hormone action. This may explain normal thyroid-stimulating hormone (TSH) levels despite reduced circulating T3 in patients on long-term phenytoin.

    Area of Science:

    • Endocrinology
    • Pharmacology
    • Molecular Biology

    Background:

    • Long-term phenytoin use is associated with reduced circulating free thyroid hormone levels.
    • Despite reduced thyroid hormone levels, patients on phenytoin typically maintain a normal clinical euthyroid state and serum TSH concentration.
    • This discrepancy suggests phenytoin may interfere with the cellular actions of thyroid hormones.

    Purpose of the Study:

    • To investigate the direct effect of phenytoin on thyroid hormone action within the pituitary gland.
    • To determine if phenytoin influences the binding of tri-iodothyronine (T3) to nuclear receptors in pituitary cells.

    Main Methods:

    • Isolated nuclei from rat anterior pituitary tissue were used to study T3 binding.
    • The effect of phenytoin on T3 nuclear binding was assessed in a dose-dependent manner.

    Related Experiment Videos

  • Thyroid-stimulating hormone (TSH) release from cultured rat anterior pituitary cells was measured following stimulation with thyrotrophin-releasing hormone (TRH) in the presence of phenytoin.

    • Main Results:

    • Phenytoin demonstrated a dose-dependent inhibition of T3 binding to pituitary cell nuclei.
    • Phenytoin partially inhibited TRH-stimulated TSH release from cultured pituitary cells.
    • These findings indicate a direct interaction of phenytoin with the T3 nuclear receptor pathway in thyrotrophs.

    Conclusions:

    • Phenytoin directly affects thyroid hormone action at the pituitary level.
    • The mechanism involves interference with nuclear T3 receptor binding in thyrotrophs.
    • This direct pituitary effect likely contributes to the maintenance of normal TSH levels in patients on long-term phenytoin therapy.