Graves' disease (GD) is an autoimmune disorder and the most common cause of hyperthyroidism.2-7
In GD, thyroid stimulating immunoglobulins (TSI) bind to the TSH
receptor (TSHR) and mimic TSH stimulation of the thyroid gland. Because
TSI induced thyroid hormone secretion is not controlled by negative
feedback, such stimulation causes uncontrolled hyperthyroidism.8
Extrathyroidal manifestations of GD include endocrine exophthalmos,
pretibial myxedema. GD is characterized thyroid acropachy, i.e., the
soft-tissue swelling of the hands and clubbing of the fingers.
Radiographic imaging of affected extremities typically demonstrates
periostitis, most commonly the metacarpal bones. TSI are IgG antibodies
that can cross the placental barrier and cause neonatal thyrotoxicosis
in newborns delivered by mothers with GD.9,10
The TSH
receptor contains a large extracellular domain that presents epitopes
for a variety of autoantibodies, including TSI and Thyroid Blocking
Immunoglobulins TBI.11-13 In contrast to TSI, TBI bind to the
TSH receptor and inhibit TSH stimulation of thyroid cells, leading to
hypothyroidism. Commonly used Thyrotropin Receptor Autoantibody (TRAb)
assays do not distinguish between TSI and TBI. The IMMULITE 2000 TSI
assay utilizes recombinant human TSH receptors (hTSHR) for the specific
detection of thyroid stimulating autoantibodies.1
The clinical utility of TSI measurement includes a determination of the autoimmune etiology of thyrotoxicosis,2-7 monitoring GD patient therapy,14 prediction of remission or relapse,15 confirmation of Graves' ophthalmopathy,16 and prediction of hyperthyroidism in neonates.9,17,18
TheTSI test is used for the differential, diagnosis of etiology of
thyrotoxicosis in patients with ambiguous clinical signs or
indeterminate thyroid radioisotope scans.3 TSI can also be of
value in determining the risk of neonatal thyrotoxicosis in a fetus of a
pregnant female with active or past GD and the differential diagnosis
of gestational thyrotoxicosis versus first-trimester manifestation or
recurrence of GD.9,10 TSI can also be ordered to assess the risk of GD relapse after antithyroid drug treatment.
Several
published studies have evaluated the sensitivity and specificity of the
Siemens TSI assay for diagnosing GD patients and discriminating them
from patients with other thyroid diseases.19-22 Kembel and coworkers23
evaluated three commercially available anti-TSHR autoantibody
measurement methods and found equivalent performance in patients with
untreated GD. However, discordant results were observed when testing
specimens collected from patients undergoing treatment for GD. In these
patients, the Siemen TSI assay more frequently generated results
consistent with clinical history, results of other laboratory tests, and
imaging studies than the TSI bioassay and Roche TRAb assay. In the
validation for FDA submission,11 serum samples from 361
treated and untreated hyperthyroid Graves' disease patients, and 404
individuals with other thyroid or autoimmune diseases were evaluated.
The TSI values for patients without GD with other thyroid or autoimmune
diseases had an upper limit of 0.39 IU/L. At the 0.55 IU/L cut-off, the
clinical sensitivity and specificity for GD were 98.6% and 98.5%,
respectively.
