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helvella - Factors that interfere with thyroid tests

In common with all laboratory tests, thyroid tests can be affected by many factors. The result of this interference can range from minimal to misdiagnosis and inappropriate medications (both changes when not appropriate and not adjusting when appropriate).

This blog is simply to provide an initial look-up point. There is far more detail both in the quoted paper and elsewhere.

If you suspect interference there are several things that can be done to show that. For example, having the same tests repeated at a lab which uses a fundamentally different assay technology. Ideally, the original test would also be repeated on the same blood draw as is sent to another lab. Thus being confident the difference is due to the assay rather than that you yourself might have changed!

This paper is both reasonably up to date (July 2018) and has been cited many times.

Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm

This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3):


•    macro-TSH,
•    biotin,
•    antistreptavidin antibodies,
•    anti-ruthenium antibodies,
•    thyroid hormone autoantibodies, and
•    heterophilic antibodies.

Other possible causes of interference include:


•    TH transport proteins variants
•    Human Serum Albumin
•    TBG thyroxin-binding protein
•    TTR transthyretin
•    Drugs - including the following:

  • aspirin, 
  • furosemide, 
  • carbamazepine, 
  • phenobarbital, 
  • phenytoin, 
  • nonsteroidal anti-inflammatory agents, 
  • phenylbutazone, and 
  • heparin  
  • Tamoxifen, 
  • raloxifene, 
  • estrogen, 
  • fluorouracil, 
  • clofibrate, 
  • heroin/methadone, and 
  • mitotane 
  • nicotinic acid, 
  • asparaginase, 
  • chronic glucocorticoid therapy, and 
  • androgens/anabolic steroids

•    TSH variants
•    Paraprotein

Julien Favresse, Maria-Cristina Burlacu, Dominique Maiter, Damien Gruson, Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm, Endocrine Reviews, Volume 39, Issue 5, October 2018, Pages 830–850, https://doi.org/10.1210/er.2018-00119


https://academic.oup.com/edrv/article/39/5/830/5048350?login=false

 This paper adds warfarin as factor. (Only abstract is accessible.)

Tokumaru M, Ohba K, Kashiwabara Y, et al. Falsely elevated thyroid hormone levels associated with fibrin interference in patients receiving oral anticoagulant therapy. Annals of Clinical Biochemistry. 2023;0(0). doi:10.1177/00045632231159280

https://journals.sagepub.com/doi/10.1177/00045632231159280 

Recent research (April 2022) has shown that fasting does have a significant impact, at least on TSH. (Given that often TSH is the only test done, this could be critical.)

Effects of calorie intake and sampling time on thyroid stimulating hormone concentration 

Compared with the fasting state, the TSH level at 2 h after the calorie intake was decreased by about 30%, which might influence the diagnosis of subclinical hypothyroidism.

https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-01005-7

The above are the additional and specific factors on top of the standard things: time of day, time since dose(s) of thyroid hormones, time since change of dose, etc.

A Macro-TSH: A Clinical Diagnostic Dilemma.

EJIFCC, 12 Dec 2022, 33(4):317-324
PMID: 36605299 PMCID: PMC9768619

Abstract
Isolated increase in thyrotropin stimulating hormone (TSH) in a clinically euthyroid patient may be caused by the formation of a macromolecule between TSH and autoantibodies causing discordant thyroid function test results. Despite the effort to eliminate interferences in immunoassays, these assays are still vulnerable to different interferences. Immunoassay interferences may cause erroneous results and lead to misdiagnosis which may subject a patient to unnecessary investigations and treatment. Immunoassays are affected by multiple substances; these may be endogenous or exogenous such as heterophile antibodies, autoantibodies, macromolecules, and human anti-mouse antibodies. This case reports a 47-year-old African woman who presented with a persistent elevated TSH with thyroid hormones within normal reference limits. She was found to have a macro-TSH which was associated with IgA paraprotein.

https://europepmc.org/article/MED/36605299

 Common Interferences in Thyroid Immunoassays

https://www.endocrinologyadvisor.com/home/topics/thyroid/common-interferences-in-thyroid-immunoassays/

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[i][b]helvella - Factors that interfere with thyroid tests [/b]

A summary of factors known to interfere with thyroid tests.[/i]

https://helvella.blogspot.com/p/helvella-factors-that-interfere-with.html

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