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.

Association of thyroid dysfunction and COVID-19: A systematic review and meta-analysis

“…Low T3 syndrome, also known as the euthyroid sick syndrome (ESS) could be responsible partly for high prevalence of thyroid dysfunction in COVID-19. This syndrome is known to occur in 60 to 70% of critically ill patients regardless of the cause ( 58 ) and in different studies in admitted patients due to COVID, ESS was presented in around 30% patients(up to 64%) and were related to severity, longer hospitalization and mortality ( 40 , 59 ). Similarly, studies have suggested a significant inverse correlation between the severity of illness and low serum total T3.…”

Influence of the anti‐oestrogens tamoxifen and letrozole on thyroid function in women with early and advanced breast cancer: A systematic review

“…Depending on the target tissue, tamoxifen can have different biological actions: predominantly anti‐oestrogenic effects in the breasts, yet oestrogenic effects in the uterus and the liver. 58 Tamoxifen causes a mild increase in TBG concentrations in the liver, 58 possibly as a result of an intrinsic, enhanced oestrogen‐agonistic effect. 36 , 38 , 59 Mirzaei et al speculated on tamoxifen bind to a protein with heavier glycoside than normal TBG, reducing TBG clearance and evoking TBG increase.…”