Stepwise Approach for Use of Thyrotropin Receptor Antibody Tests

3D rendering of thyroid gland highlighted inside the neck

The American Thyroid Association guidelines accept two methods of measuring thyrotropin receptor antibody levels as optional first-line tests in the workup of thyrotoxicosis:

  • The thyroid-stimulating immunoglobulin bioassay (TSI), which detects only stimulating antibodies
  • The thyrotropin-binding inhibitory immunoglobulin assay (TBII), which measures both stimulating and non-stimulating (blocking or neutral) autoantibodies

Ellen Marqusee, MD, an endocrinologist in the Thyroid Center of the Division of Endocrinology, Diabetes and Hypertension at Brigham and Women’s Hospital, Nathalie Silva de Morais, MD, PhD, an endocrinologist formerly in the Center, and colleagues found TSI and TBII performed similarly for discriminating Graves’ disease (GD) from other causes of thyrotoxicosis. In Endocrine Practice, they add that having the two tests done simultaneously was more beneficial than TSI alone but provided little benefit compared with TBII alone.


The researchers retrospectively studied 493 adults who had active thyrotoxicosis when TBII and TSI were performed simultaneously during clinical care between May 2015 and November 2017.

Before the evaluation of antibody status, the patients were classified into three groups according to clinical findings, radionuclide uptake during thyroid scintigraphy, and histopathologic data:

  • Positive reference group—191 patients fulfilling the criteria for GD
  • Negative reference group—40 patients who did not meet the criteria for GD but fulfilled the criteria for other causes of thyrotoxicosis
  • Inconclusive group—262 patients who did not meet the criteria for either of the other groups


The principal findings were:

  • TSI and TBII were concordant in 89% of cases and were strongly correlated (ρ=0.84; P<0.01)
  • Both tests showed good specificity (95%) and high positive predictive value for GD (TSI, 98.5%; TBII, 98.6%); the sensitivities were 70% and 74%, respectively, and the negative predictive values were 40% and 43%
  • The combination of TSI and TBII was 81% accurate in diagnosing GD, whereas TBII alone was 77.5% accurate
  • 21% of patients in the positive reference group tested negative on both TSI and TBII, whereas 8% of patients in the negative reference group had at least one positive TSI or TBII test
  • The risk of a false-negative result was higher in patients with subclinical hyperthyroidism, longstanding thyrotoxicosis, absence of goiter or Graves’ ophthalmopathy, and, particularly, normal radionuclide uptake

Guidance for Patient Care

In the initial workup in the evaluation of patients with active thyrotoxicosis:

  • TBII performed alone is slightly more accurate than TSI performed alone
  • A positive TBII result is sufficient for a confident GD diagnosis (keeping in mind that some individuals with transient thyroiditis may manifest thyroid-stimulating hormone receptor autoantibodies)
  • A negative TBII result does not exclude GD, especially in patients with mild or longstanding hyperthyroidism
  • The combination of TSI and TBII could be reserved for patients with normal radionuclide uptake, subclinical thyrotoxicosis, no goiter, no Graves’ ophthalmopathy, and a longstanding clinical presentation

The results of either assay should be carefully interpreted in conjunction with other clinical information.

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