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Orphenadrine (Disipal), serum thyroxine and thyroid function

W M Wiersinga, A J Fabius, J L Touber

Acta Endocrinologica

|November 1, 1977

Summary

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Orphenadrine, up to 300 mg daily, does not affect thyroid function. It falsely elevates serum thyroxine levels measured by competitive protein binding due to drug metabolites interfering with the assay.

Area of Science:

Endocrinology
Pharmacology

Background:

Orphenadrine is a medication with anticholinergic properties.
Its potential impact on thyroid hormone levels requires investigation.

Purpose of the Study:

To determine if orphenadrine influences thyroid function in humans.
To investigate the mechanism behind observed changes in serum thyroxine measurements.

Main Methods:

Administered orphenadrine to volunteers and patients, with dosage escalation and discontinuation.
Measured various thyroid function tests including PBI, RT3U, TT3, TSH, and TRH response.
Assessed serum thyroxine using competitive protein binding (CPB) and radioimmunoassay (RIA) techniques.
Performed in vitro assays with orphenadrine and its metabolites.

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Main Results:

No significant changes in PBI, RT3U, TT3, TSH, or TRH response were observed.
Orphenadrine significantly increased serum thyroxine levels measured by CPB (P < 0.001).
Serum thyroxine levels measured by RIA were not affected.
In vitro studies indicated orphenadrine metabolites competed with thyroxine for binding sites.

Conclusions:

Orphenadrine, at therapeutic doses up to 300 mg/day, does not alter intrinsic thyroid function.
The observed increase in serum thyroxine by CPB assay is an artifact caused by orphenadrine metabolites.
These metabolites interfere with thyroxine binding globulin in the CPB assay, leading to falsely elevated results.