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A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.
A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.
A 50-year-old woman returns for routine follow-up. She has a 15-year history of hypothyroidism, pernicious anemia, and celiac disease. She has had some recent abdominal pain, but no changes in her bowel patterns, and she has not experienced any problems with chest pain, palpitations, or weakness recently. The only medication she is taking is levothyroxine 125 mcg. She has reported no recent weight loss, her blood pressure is 100/60 mm Hg, pulse is 66 beats per minute, temperature is 36.8 degrees Celsius, body mass index is 20, and she does not have a neck goiter. Her cardiac exam was normal and her neurological exam revealed no tremor. Her lab for thyroid-stimulating hormone (TSH) was less than 0.03, and her lab for free thyroxine (FT4) was 2.2, while her TSH level had been 1.4 a year ago. Her levothyroxine dose was decreased to 100 mcg/day, and her repeat lab for TSH, which occurred 12 weeks later, was still less than 0.03. What is the best explanation for why this patient’s labs look like hyperthyroidism, but this patient clinically does not appear to have hyperthyroidism?
A) She was initially given too much levothyroxine; her TSH response is lagging to dose reduction.
B) She has Graves’ disease.
C) She has acute thyroiditis.
D) She is taking extra thyroid hormone.
E) She is taking biotin.
This patient has a history that includes multiple autoimmune diseases including hypothyroidism. It would be extremely unlikely that she would develop Graves' disease or develop acute thyroiditis in the setting of a gland that has been underfunctioning for years. She has no symptoms suggesting that she has hyperthyroidism, which makes taking more thyroid hormone than she is reporting less likely, although this could be possible. The TSH response can lag after dose adjustments of thyroid, but usually a 6-week interval is adequate. This patient’s testing was done 12 weeks after dose reduction making this very unlikely.
The cause for the labs that look like hyperthyroidism in this patient who appears clinically euthyroid is that she is taking biotin. Biotin (vitamin B7) has become a very popular supplement in the past few years for thin hair, brittle nails, and fatigue. The RDA for biotin is 30 mcg. It is widely available in high doses – 5,000-10,000 mcg – which are common doses for supplements.
Biotin has been used extensively as a key component of immunoassays. Streptavidin, a protein produced by the bacteria Streptomyces avidinii, binds biotin with an extremely high affinity, and this binding is utilized in a number of immunoassays, including the assays for thyroid hormone and TSH.1
High serum levels of biotin can make the assays inaccurate, with lower-than-actual TSH and higher-than-actual thyroid hormone levels. Multiple case reports have documented this happening clinically.1-3 I personally saw a case of this recently in my practice. Katzman and colleagues looked at the prevalence of biotin use in outpatients.4 They found that 7.7% were taking supplemental biotin, while 7.4% had levels of biotin in serum samples that were at a level that could interfere with biotin-based serum assays.
Theoretically, biotin can affect multiple other assays that use the streptavidin-biotin assay. The most concerning of these potential problems is with troponin assays. Biotin can falsely lower troponin assays and this can lead to missing the diagnosis of cardiac injury. The Food and Drug Administration released a warning about this and other biotin lab interactions in November 2017.5 Several studies have demonstrated that this effect can occur at serum levels achievable with available over-the-counter doses of biotin.6,7
Not all troponin assays are affected by high serum levels of biotin: The Gen 5 cTnT assay is the only troponin assay affected.7 I could not find any case reports that have been published where biotin had caused a clinical missed diagnosis with troponins.
Pearls
Consider biotin supplement use when you have patients whose labs look like hyperthyroidism, but clinically do not appear to be hyperthyroid.
Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. Contact Dr. Paauw at [email protected].
References
1. Charles S, Agrawal N, and Blum M. Erroneous thyroid diagnosis due to over-the-counter biotin. Nutrition 2019;57:257-8.
2. Elston MS et al. Factitious Graves’ disease due to a biotin immunoassay interference – a case and review of the literature. J Clin Endocrinol Metab 2016;101:3251-5.
3. Barbesino G. Misdiagnosis of Graves ’disease with apparent severe hyperthyroidism in a patient taking biotin megadoses. Thyroid 2016;26(6):860-3.
4. Katzman et al. Prevalence of biotin supplement usage in outpatients and plasma biotin concentrations in patients presenting to the emergency department. Clin Biochem. 2018 Sep;60:11-16.
5. “The FDA Warns that Biotin May Interfere with Lab Tests: FDA Safety Communication,” Nov. 28, 2017.
6. Trambas et al. Characterization of the scope and magnitude of biotin interference in susceptible Roche Elecsys competitive and sandwich immunoassays. Ann Clin Biochem. 2018 Mar;55(2):205-15.
7. Frame IJ et al. Susceptibility of cardiac troponin assays to biotin interference. Am J Clin Pathol. 2019 Apr 2;151(5):486-93.