Biochemical Hyperthyroidism in a Newborn Baby Caused by Assay Interaction from Biotin Intake

Pedersen, Inge Bülow; Laurberg, Peter

doi:10.1159/000448034

Cited by 23 publications

(7 citation statements)

References 10 publications

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“…In the last year, numerous case reports have documented interference in patients for whom high-dose biotin is either an established or emerging therapy, namely in the setting of biotin-responsive inborn errors of metabolism and multiple sclerosis (MS), respectively. [4][5][6][7][8][9][10][11] There is also growing concern that the increased availability of over-the-counter 'mega'-biotin supplements may have introduced the risk of interference into the general population, 9,12,13 although the prevalence of this is unknown.…”

Section: Introductionmentioning

confidence: 99%

Depletion of biotin using streptavidin-coated microparticles: a validated solution to the problem of biotin interference in streptavidin–biotin immunoassays

Trambas¹,

Yen

et al. 2017

Ann Clin Biochem

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Background Biotin interference in streptavidin-based immunoassays causes widespread analytical distortions that may lead to clinical confusion, inappropriate patient management and, ultimately, adverse events. Its prevalence has increased recently due to the increased use of high-dose biotin therapy in specific patient groups (notably multiple sclerosis) and possibly the general community. Methods We have developed a method to deplete biotin from samples using the streptavidin-coated magnetic microparticles that are a component of most susceptible assays. Results We show that high concentrations of spiked biotin can be adequately depleted from serum using this approach, and that gross biochemical derangements can be restored to normality. We also show that biotin in samples derived from multiple sclerosis patients receiving 300 mg biotin daily can be adequately depleted to remove associated analytical interference and restore normal results. The method is applicable to competitive and sandwich immunoassays and importantly, because it does not change the volume of the sample, suitable for the measurement of free thyroid hormone assays. Application of the method does not significantly change the precision of measurement, and for the majority of analytes, the accuracy is not substantially altered. Conclusions Adopting this method enables laboratories to confirm biotin interference in the appropriate clinical setting. Moreover, it enables laboratories to remove the interference and report accurate and reliable results, without the need for patients to withhold beneficial therapy prior to blood tests. Until the biotin tolerance of susceptible assays is improved, our method gives laboratories a safe alternative for reporting results using streptavidin-based methods.

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Section: Introductionmentioning

confidence: 99%

Depletion of biotin using streptavidin-coated microparticles: a validated solution to the problem of biotin interference in streptavidin–biotin immunoassays

Trambas¹,

Yen

et al. 2017

Ann Clin Biochem

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“…The patients most vulnerable to interference were those with rare inborn errors of metabolism for which high-dose biotin therapy is an established treatment, 4 such as biotinidase deficiency, holocarboxylase synthetase deficiency and biotin-thiamine-responsive basal ganglia disease. 3,[5][6][7][8] In the last year, however, highdose biotin therapy has been adopted as a promising new treatment for progressive multiple sclerosis (MS). 9,10 With a worldwide prevalence that far exceeds the combined prevalence of the above-mentioned metabolic disorders, MS is not a rare disease: the global median prevalence is 33/100,000, but higher with increasing distance from the equator.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays

Trambas¹,

Yen

et al. 2017

Ann Clin Biochem

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Background Biotin interference is a significant problem to which at-risk laboratories must now be attuned. We sought to systematically characterize the nature of this interference in Roche immunoassays. Methods Known concentrations of biotin were titrated into serum samples and the effects on competitive and sandwich immunoassays were analysed. The maximum and minimum concentrations examined reflect those likely to be achieved in individuals on 5 to 10 mg supplements at the lower end, and 100 to 300 mg biotin at the high end. Results A high variability in biotin tolerance was observed. Some assays, such as troponin T, TSH and antithyroid antibodies, were extremely sensitive to the lower concentrations of biotin (15.6 and 31.3 ng/mL), whereas the majority of assays were relatively resistant. At concentrations ≥500 ng/mL, all assays showed significant interference from biotin but, again, the magnitude of the interference was variable. The more sensitive assays showed profound analytical bias at biotin concentrations that occur with high-dose therapy. Conclusion Our data demonstrate high variability in biotin tolerance across Roche immunoassays. The shape of the dose-response curves provides more detailed information than the single manufacturer-quoted figure for biotin tolerance. Accordingly, these data may be used by laboratories for more accurate risk assessment in predicting the effects of biotin. Our data may also be extrapolated to guide timing of blood tests in patients on high-dose biotin therapy: it demonstrates the number of half-lives required to withhold biotin in order to decrease its concentration to below a given assay tolerance.

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“…An increase in the measured concentrations of both free T3 and free T4 was present. Both concentrations peaked around two hours after ingestion, and the increase lasted for at least 24 hours [ 9 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of High-dose Biotin on Thyroid Function Tests: Case Report and Literature Review

Ardabilygazir¹,

Afshariyamchlou²,

Mir³

et al. 2018

Cureus

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Biotin is a readily available supplement that is part of the B-complex vitamins. It is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. The recommended daily intake (RDI) of biotin ranges from 30 to 70 mcg per day. At high doses (10,000 times RDI), biotin improves clinical outcomes and quality of life in patients with progressive multiple sclerosis (MS). It has been reported to cause interference in immunoassays resulting in abnormal thyroid function tests. Hereby we are describing the case of a patient having MS who was on high-dose biotin, seen in the clinic for a follow-up visit with thyroid function tests suggestive of Graves’ disease with no signs and symptoms of hyperthyroidism and completely normal physical examination. In the case we have described, the laboratory measurements suggestive of thyrotoxicosis were attributed to interference of the patient’s high-dose biotin treatment with the biotin-streptavidin chemistry of the immunoassays. We observed normalization of the thyroid stimulating hormone (TSH) and free T4 measurements when the patient withheld biotin for a week. As our case illustrates, early consideration of biotin interference minimizes unnecessary repeat laboratory studies. As trials in MS are progressing, we expect to see more patients on high-dose biotin treatment with spurious laboratory measurements. Therefore, we advise careful history taking and close communication with the laboratory when the clinical picture does not match with the laboratory results.

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Biochemical Hyperthyroidism in a Newborn Baby Caused by Assay Interaction from Biotin Intake

Abstract: We describe a case of biochemical neonatal thyrotoxicosis caused by biotin supplementation. Biotin may interact with thyroid function testing to imitate thyrotoxicosis with low thyroid-stimulating hormone and elevated triiodothyronine and thyroxine levels.

Cited by 23 publications

References 10 publications

Depletion of biotin using streptavidin-coated microparticles: a validated solution to the problem of biotin interference in streptavidin–biotin immunoassays

Depletion of biotin using streptavidin-coated microparticles: a validated solution to the problem of biotin interference in streptavidin–biotin immunoassays

Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays

Effect of High-dose Biotin on Thyroid Function Tests: Case Report and Literature Review

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