Is a storm coming? Dr Howard Gerson, PGY-5 Jewish General Hospital / McGill University
Disclosures • None
Clinical Dilemma • 65yoM with long-standing multiple sclerosis, atrial fibrillation, non- ischemic cardiomyopathy presents to his Cardiologist for several weeks of increasing SOB • Exam: weight gain, pitting pedal edema • Dx: CHF • Plan: Increase diuretics, find precipitant
A diagnostic test was performed • Thyroid function tests; • TSH 0.05 mU/L (0.4 – 4.5) • fT4 68 pmol/L (9 – 26) • Consult Endocrinology!
How peculiar • You are not; • Tachycardia, hyperthermic, hypertensive • Diaphoretic, tremulous, obtunded • You have normal; • Reflexes • Thyroid gland (by exam and US) • There is no; • Graves ophthalmopathy or dermopathy • The diuretics seemed to have corrected the weight gain, edema, SOB • Plan: Repeat the bloodwork!
I guess labs don’t lie • Thyroid function tests; • TSH 0.02 mU/L (0.4 – 4.5) • fT4 >100 pmol/L (9 – 26) • fT3 13.8 pmol/L (2.8 – 7.1) • Anti-TPO >600 IU/mL (0 – 35) • Anti-TSH receptor >40 U/L (0 – 1.2) • Dx: Graves? • Plan: Start methimazole, follow
I guess labs don’t lie • Follow-up over 2 months; • Thyroid function appears to be normalizing • Still, seems odd he has been clinically euthyroid throughout • Plan: Consult Medical Biochemistry
What beautiful hair & nails you have! • This patient is on high-dose biotin for MS! • Biotin is also a ‘naturopathic’ remedy for brittle nails & hair • Daily requirement = 30 mcg • Many lab tests use biotin…are his supplements interfering with the assays? • Plan: Given his good clinical status lets stop methimazole & biotin, re-test
Do labs lie? • Thyroid function results normalize • Was he becoming hypothyroid then on methimazole? • Anti-TPO and anti-TSH receptor results are now normal
Immunoassays • Many take advantage of biotin – streptavidin interaction to join analytes and the antibodies used to quantify them • One of the strongest non-covalent interactions known • Dissociation constant ~ 10 15 !! • 1000 - 100,000x stronger than normal analyte-antibody interactions • Two main types of immunoassays; 1. Sandwich – potential negative bias from biotin 2. Competitive – positive bias
Immunoassays Images from Roche Diagnostics
Immunoassays Images from Roche Diagnostics
Immunoassays Signal detected Analyte concentration Images from Roche Diagnostics
Immunoassays Signal detected Analyte concentration Images from Roche Diagnostics
Immunoassays Signal detected Analyte concentration Signal detected Analyte concentration Images from Roche Diagnostics
Immunoassays Signal detected Analyte concentration Signal detected Analyte concentration Images from Roche Diagnostics
I guess labs don’t lie…or maybe they do? • Thyroid function tests; • TSH 0.02 mU/L (0.4 – 4.5) -- Sandwich • fT4 >100 pmol/L (9 – 26) -- Competitive • fT3 13.8 pmol/L (2.8 – 7.1) -- Competitive • Anti-TPO >600 IU/mL (0 – 35) -- Competitive • Anti-TSH receptor >40 U/L (0 – 1.2) -- Competitive • Dx: Factitious Graves secondary to biotin supplements
Immunoassays • Interference NOT limited to thyroid; • ANY analyte measured by a biotin based immunoassay can be affected
Take away • Consider non-pathologic differentials in addition to pathologic ones • Especially when the biochemistry does not match the clinical picture • Important for healthcare professionals to collaborate • Medical Biochemists are available for consult
Questions? • For further information please consider; • Elston MS et al. Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature. J Clin Endocrinol Metab 2016;101(9):3251-3255 • Samarasinghe S et al. Biotin Interference With Routine Clinical Immunoassays: Understand the Causes and Mitigate the Risks. Endocr Pract 2017 (in press) • Acknowledgement; • Dr Shaun Eintracht, Jewish General Hospital
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