Falsely Undetectable TSH in Four Commonly Used Immunoassays: A Possible Novel Human TSH Variant?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 449-497-Thyroid Neoplasia & Case Reports
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-467
Julia C Drees*1, Judith A Stone1, C Randy Reamer2, Victoria E Arboleda2, Karl Huang1, Jane Hrynkow1, Carolyn Hoke1, Thomas S Lorey1 and Richard S Dlott3
1Kaiser Permanente, Berkeley, CA, 2Siemens Healthcare Diagnostics, Tarrytown, NY, 3The Permanente Medical Group, Martinez, CA

The accuracy and precision of TSH immunoassays are generally considered sufficiently reliable to support screening and therapeutic monitoring of thyroid dysfunction in humans based on TSH results alone. Low TSH results due to functionally compromising TSH mutations have previously been described.  We have identified 16 individuals with functional TSH that is falsely undetectable by four widely used FDA-approved TSH immunoassays from a single vendor.


An index case of a clinically euthyroid woman with discordant TSH results was recognized by a physician at our institution. The patient had undetectable TSH on our standard TSH assay and normal TSH on a different assay. Prospective and retrospective strategies were used to identify additional cases. Prospectively, all samples with TSH results <0.01 IU/mL on our standard assay were reflexed to a second assay. Discordant samples underwent further TSH analysis on up to six additional FDA-approved immunoassays. Retrospectively, thyroid function test results from 1.6 million individuals were analyzed to identify possible discordant cases and correct medical records. Hybrid TSH assays were built to identify which antibodies failed to bind TSH in these individuals.


16 individuals (14 euthyroid and 2 hypothyroid), all but one of South Asian descent, have been identified with falsely undetectable TSH (<0.01 IU/mL) in four of eight commercially available TSH assays. In all cases, the clinical assessments, free T4, and T3 results of these individuals are consistent with the normal or elevated TSH results. Specific antibodies failing to detect TSH in these cases were identified in the four affected assays.


To date, 16 cases have been identified out of approximately two million Kaiser Permanente members in Northern California; we estimate a maximum prevalence of 0.005% in our population. We suspect these individuals have a previously unrecognized, functionally normal, TSH variant to which some monoclonal antibodies fail to bind. Incorrect undetectable TSH results were reported for 14 of the 16 individuals; nine of these individuals were initially treated based on repeated undetectable TSH values, in many cases despite normal free T4 and normal thyroid scans. Health care providers should be aware that rare individuals may have falsely undetectable TSH results in some hyper-selective TSH immunoassays; this should be considered when using TSH as the sole diagnostic test for thyroid dysfunction.

Disclosure: CRR: Employee, Siemens Healthcare Diagnostics. VEA: Employee, Siemens Healthcare Diagnostics. Nothing to Disclose: JCD, JAS, KH, JH, CH, TSL, RSD

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm