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Erroneous thyroid diagnosis due to over-the-counter biotin

Charles, Stephanie; Agrawal, Nidhi; Blum, Manfred
OBJECTIVES/OBJECTIVE:Biotin is a component of the vitamin B complex used in standard immunoassays to detect serum levels of various hormones and non-hormones, including thyrotropin (TSH) and thyroxine. These assays involve a strong bond between streptavidin and biotin, which serves as an anchor for measured analytes. Large doses of exogenous biotin for the treatment of certain medical conditions have resulted in assay interference, causing TSH to be spuriously lowered. Smaller doses of biotin found in dietary supplements also have caused assay interference. METHODS:We describe four cases in which over-the-counter (OTC) biotin caused erroneous thyroid diagnosis and clinical confusion in patients with preexisting thyroid disease. Serum TSH and thyroxine were measured by the Vitros 5600 assay. CONCLUSIONS:Although the biotin-streptavidin interaction is sensitive for detecting serum levels of TSH, it is subject to interference by exogenous biotin at levels found in OTC products. The widespread use of OTC biotin for cosmetic purposes can adversely affect the diagnosis of the entire spectrum of functional thyroid disorders. Physicians must carefully and routinely question for the use of biotin before thyroid function testing.
PMID: 30199718
ISSN: 1873-1244
CID: 3278152

Erroneous thyroid diagnosis and management due to overthe-counter biotin [Meeting Abstract]

Charles, S; Agrawal, N; Blum, M
Biotin is a small B vitamin that is used in standard immunoassays to detect serum levels of various hormones, including TSH (1). Recent reports have demonstrated that large doses of exogenous biotin can interfere with the immunoassay, causing euthyroid patients to appear biochemically hyperthyroid (2). In the fall of 2016 one Endocrinology practice encountered four consultations in which over-the-counter (OTC) biotin caused erroneous TSH measurement, leading to clinical confusion and the potential for improper management. (1) Sub-acute thyroiditis (SAT) masquerading as thyrotoxicosis. A 78 year-old woman with a remote history of SAT was referred because depressed TSH 0.2 mIU/L (0.5-5.0 mIU/L) suggested disease recurrence. She was asymptomatic and clinically euthyroid; she revealed she was taking a biotin supplement. TSH rose to 2.8 mUI/L (0.5-5.0 mIU/L) 72 hours after biotin was stopped. (2) Non-toxic goiter confused for toxic nodular goiter (TNG). A 69 year-old woman was diagnosed with TNG as her TSH was low 0.167 mUI/L (0.5-5.0 mIU/L). She was referred for treatment with radioactive iodine (I-131). She reported using an OTC biotin supplement containing 300 mcg for "thinning hair." Repeat TSH days after stopping biotin was 0.937 mUI/L (0.5-5.0 mIU/L). (3) Sub-clinical hypothyroidism mistaken for Graves' disease. An 84 year-old woman reported excess fatigue and depression. However, TSH was low 0.13 mIU/L (0.5-5.0 mIU/L), FT4 was normal, and the serum was positive for anti-thyroglobulin antibody and negative for anti-TPO antibody. I-131 therapy was entertained for presumed Graves' disease. The patient admitted to using over-the-counter biotin for "nail breakage." After biotin was stopped, TSH rose to 5.5 mIU/L (0.5-5.0 mIU/L). Given her symptoms, positive antibodies, and elevated TSH off of biotin, the patient was diagnosed with sub-clinical hypothyroidism due to Hashimoto's thyroiditis and prescribed levothyroxine. (4) Stable Hashimoto's thyroiditis mistaken for progression to Graves' disease. A 66 year-old woman with a past diagnosis of Hashimoto's thyroiditis had been taking OTC biotin intermittently. Recent thyroid tests revealed low TSH 0.193 mIU/l (0.5-5.0 mIU/L) with normal T3 and Free T4. There was concern for progression to Graves' disease. Repeat TSH testing off biotin was normal. In conclusion, while the biotin-streptavidin immunoassay is sensitive for detecting serum levels of TSH (1), it is subject to interference by exogenous biotin at levels found in OTC supplements 1000 times smaller than previously reported (2). Our case series shows that the widespread use of OTC biotin for cosmetic purposes can adversely affect the diagnosis and management of the entire spectrum of functional thyroid disorders. Physicians must carefully and routinely question for the use of this supplement to ensure that patients with thyroid disorders are correctly diagnosed and managed
ISSN: 0163-769x
CID: 2632022


Blum, Manfred; Agrawal, Nidhi; Friedman, Kent
PMID: 27295012
ISSN: 1530-891x
CID: 2144992

In Thyroidectomized Thyroid Cancer Patients, False-Positive I-131 Whole Body Scans Are Often Caused by Inflammation Rather Than Thyroid Cancer

Garger, Yana Basis; Winfeld, Mathew; Friedman, Kent; Blum, Manfred
Objective. To show that I-131 false-positive results on whole-body scans (WBSs) after thyroidectomy for thyroid cancer may be a result of inflammation unassociated with the cancer. Methods. We performed a retrospective image analysis of our database of thyroid cancer patients who underwent WBS from January 2008 to January 2012 to identify and stratify false positives. Results. A total of 564 patients underwent WBS during the study period; 96 patients were referred for 99 I-131 single-photon emission computed tomography (SPECT/CT) scans to better interpret cryptic findings. Among them, 73 scans were shown to be falsely positive; 40/73 or 54.7% of false-positive findings were a result of inflammation. Of the findings, 17 were in the head, 1 in the neck, 4 in the chest, 3 in the abdomen, and 14 in the pelvis; 1 had a knee abscess. Conclusions. In our series, inflammation caused the majority of false-positive WBSs. I-131 SPECT/CT is powerful in the differentiation of inflammation from thyroid cancer. By excluding metastatic disease, one can properly prognosticate outcome and avoid unnecessary, potentially harmful treatment of patients with thyroid cancer.
PMID: 26977418
ISSN: 2324-7096
CID: 2031392

I-131 SPECT/CT Elucidates Cryptic Findings on Planar Whole-Body Scans and Can Reduce Needless Therapy with I-131 in Post-Thyroidectomy Thyroid Cancer Patients

Blum, Manfred; Tiu, Serafin; Chu, Michael; Goel, Sumina; Friedman, Kent
Background: Interpreting I-131 whole-body scans (WBSs) after thyroidectomy for thyroid cancer is not simple. There are scans in which interpretation is speculative because of cryptic findings (CF). Complexity is added in scans that are done a week after an ablative or therapeutic dose of I-131 because not only is I-131-labeled thyroxine (T4) distributed throughout the body, but inorganic I-131 that is derived from the de-iodination of T4 may be also detected. We present our observations regarding the analysis of CF on WBS using I-131 single-photon emission computed tomography (SPECT) in fusion with noncontrast computed tomography (CT), referred to here and elsewhere as I-131 SPECT/CT. Methods: Forty of 184 WBSs in 38 thyroidectomized thyroid cancer patients were followed up with I-131 SPECT/CTs. The SPECT/CT images were acquired after a tracer dose of I-131 (n=82) or a week after an ablative or therapeutic dose of I-131 (n=102). Results: Among 184 WBSs, 40 (22%) had CF. In 35 patients the WBS was negative for metastatic disease except for the CF and 5 patients had evidence of thyroid cancer in addition to the CF. There were 49 CF in the planar scans that were localized by SPECT/CT. These were characterized as physiological uptake in gingiva, thymus, gall bladder, menstrual blood, uterine fibroid, recto-sigmoid, colon, and bladder. Also observed was uptake in sites that represented nonthyroidal pathology including dental abscess, hiatal hernia, renal cyst, and struma ovarii. SPECT/CT suggested that 10 of the CF were actually of thyroid origin. In 40 SPECT/CT scans, the images contributed to interpreting the scan. In 15 of 40 patients the SPECT/CT analysis of WBS was performed with tracer doses of I-131 and was important for determining whether to administer ablative I-131 treatment. In another 25 patients, in whom SPECT/CT was performed after ablative or therapeutic doses of 131-I, information regarding the characterization of CF by SPECT/CT was useful in determining if thyroid cancer metastases or thyroid remnants were present. Conclusions: I-131 SPECT/CT is a useful tool to characterize atypical or CF on WBS by differentiating thyroid remnant or cancer from physiologic activity or nonthyroid pathology. In the past, uptake on a WBS that was not explicable as physiologic activity was identified as putative or possible thyroid cancer and generally was treated with I-131. Now, by identifying activity in some possible cancer sites as not thyroid cancer, SPECT/CT can reduce inappropriate treatment with I-131. SPECT/CT of WBS performed after ablative doses of 131-I is useful in determining the nature of CF and therefore likely providing prognostic information
PMID: 22007920
ISSN: 1557-9077
CID: 141075

Radioactivity of blood samples taken from thyroidectomized thyroid carcinoma patients after therapy with (131)i

Larkin, Ann; Millan, Evelyn; Noz, Marilyn; Wagner, Steve; Friedman, Kent; Blum, Manfred
Background: Occasionally, blood samples may be required from thyroid cancer patients after they have been given the therapy dose of (131)I, as part of necessary medical management of comorbidities. Thus, in the days after (131)I administration, medical health professionals may be involved in the withdrawal, handling, and manipulation of radioactive blood samples. The purpose of this study was to quantify the amount of radioactivity in blood samples taken from thyroidectomized thyroid carcinoma patients after the administration of therapeutic activities of (131)I. Methods: For dosimetry purposes, serial blood sampling is performed on thyroidectomized thyroid carcinoma patients prior to therapy with (131)I. The quantities of radioactive material present in these blood samples were expressed as a percentage of the administered activity and then extrapolated to the high levels of (131)I used in therapy for 377 patients in this study. The corresponding radiation exposure rate from the blood samples was then calculated to determine what radiation protection methods were required for staff handling these samples. Results: The average amount of radioactivity in a 1 mL blood sample at 1 hour postadministration of 5.5 GBq (150 mCi) of (131)I was 0.2 +/- 0.15 MBq (5.4 +/- 4.0 muCi). This corresponds to an exposure rate of 1.23 muSv/h (0.123 mrem/h) at 10 cm from the sample. For samples obtained beyond 24 hours after a therapeutic administration of 5.55 GBq (150 mCi), the exposure levels are approximately equal to background radiation. Conclusion: The data in this study indicate that the radiation exposure from blood samples withdrawn from thyroidectomized thyroid cancer patients is low. However, to ensure that staff members are exposed to minimal levels of radiation, it is imperative that staff members who are involved in withdrawing, handling, or manipulating radioactive blood samples adhere to the recommended radiation safety practices
PMID: 21834682
ISSN: 1557-9077
CID: 137003

Lithium carbonate use may enhance hypercalcemia in a patient with primary hyperparathyroidism [Meeting Abstract]

Huberman, D T; Blum, M
Case presentation: This 70 year old woman who has been taking Lithium Carbonate (Li) for several years for bipolar disorder had been normocalcemic 2 years ago. There was recent, severely altered sensorium associated with hypercalcemia of 13.5mg/dL (Ca) and high iPTH(152pg/mL). The hypercalcemia was refractory to copious hydration (4 L water/day). Other laboratory assessment was unremarkable. After transfer to NYU Langone Medical Center a 1.3cm parathyroid adenoma (PA) was resected. Intra-operatively the iPTH fell from 117.6 to 24.8pg/mL but Ca remained 10.2 mg/dL for 2 days, and has remained normal since. The patient's psychiatrist felt that cessation of Li would be extremely ill advised, so the medication was continued.Discussion: There are 2 main mechanisms by which Li causes hypercalcemia: 1)Li enhances PTH secretion by decreasing parathyroid gland sensitivity to calcium. 2)Li increases urinary calcium reabsorption and decreases urinary calcium excretion. Reports have shown in Li treated patients an increase in mean parathyroid gland volume, four gland hyperplasia,and PA. It is not known whether Li use leads to the formation of PA, or unmasks asymptomatic, undetected PA.Nephrogenic diabetes insipidus is the most common renal side effect associated with chronic Li use. It is likely that Li accumulates in the collecting tubules and then interferes with the action of anti diuretic hormone. The resultant polyuria in a patient with Li induced nephrogenic diabetes insipidus may further exacerbate a patient's hypercalcemia. Li-induced polyuria is associated with decreased renal medullary sodium and osmolality, and defective renal urinary concentrating ability, which may have contributed to hypercalcemia that was refractory to aggressive hydration in our patient. Hence, hydration with sodium-rich fluid might have been beneficial. Conclusions: We report a case of significant hypercalcemia that was resistant to copious hydration and lagged behind adenoma resection in a patient with primary hyperparathyroidism (HPT) and chronic Li use. Lessons include the need for caution in the use of Li in a HPT patient with bipolar disorder, consideration of discontinuing Li when a HPT patient has an unusually high calcium level, and attention to the use of sodium-rich hydration to manage hypercalcemia
ISSN: 0163-769x
CID: 159279

Somatostatin receptor scintigraphy as a potential diagnostic and treatment modality for thyroid follicular-cell-derived cancers [Letter]

Margulies, Debra J; Blum, Manfred
PMID: 20553198
ISSN: 1557-9077
CID: 134421

PET and PET/CT of thyroid disease

Chapter by: Friedman, Kent P; Blum, Manfred
in: Positron emission tomography computed tomography : a disease-oriented approach by Kramer, Elissa Lipcon; Ko, Jane P; Ponzo, Fabio; Mourtzikos, Karen [Eds]
New York : Informa Healthcare, 2008
pp. ?-?
ISBN: 0849380871
CID: 1465262

Ultrasonic imaging and identification of metastases in cervical lymph nodes

Chapter by: Blum, Manfred
in: Thyroid cancer : a comprehensive guide to clinical management by Wartofsky, L; Van Nostrand, Douglas [Eds]
Totowa, N.J. : Humana Press, c2006
pp. 351-358
ISBN: 9781592599950
CID: 845852