Abnormal thyroid test results in euthyroid state: An appraisal of the
role of drugs
Abstract
Background: Thyroid function tests (TFTs) are one of the most frequently
performed hormonal tests. Abnormal reports are commonly encountered even
in the absence of thyroid dysfunction with medication use during testing
being an important cause of this anomaly. Knowledge about the effects of
different drugs on various components of TFTs will prevent unnecessary
referrals, investigation and potentially dangerous therapeutic
decisions. Objective: This narrative review aims to provide information
to physicians regarding how various medicines can alter results of TFT
even in the euthyroid state. Methods: Articles published up to April,
2020 in English language were identified through searches in PubMed and
Google Scholar with a search strategy using keywords appropriate to
analyze the effects of different medications on thyroid assays. Results:
Medications ranging from over-the-counter vitamins to anti-cancer drugs
are associated with anomalous TFTs in euthyroid individuals. This occurs
through mechanisms of assay interference and alterations in levels or
affinity of thyroid binding proteins (TBPs). High-dose biotin can mimic
findings seen in thyrotoxicosis by interference with immunoassays
utilizing streptavidin-biotin immobilizing systems. Heparin-induced
increase in non-essential fatty acid causes displacement of thyroxine
(T4) from TBP, effecting an artefactual increase in free hormone levels.
Increases or decreases in thyroid-binding globulin (TBG), the key TBG,
can cause a corresponding change in total T4 and tri-iodothyronine
levels. Estrogen, selective estrogen receptor modulators,
5-fluorouracil, mitotane, clofibrate, heroin and methadone can increase
while androgens, anabolic steroids, glucocorticoids, nicotinic acid and
l-asparaginase can decrease TBG. Salicylates, frusemide, carbamazepine
and phenytoin may displace T4 from TBP, producing a decline in the total
hormone levels. Conclusions: Many categories of medications can
interfere with analysis of TFTs through different mechanisms. Awareness
about these drug-induced TFT fallacies is essential to avoid improper
diagnosis and overtreatment of euthyroid patients.