TSI Test

Thyroid-Stimulating Immunoglobulin (TSI) is a specific type of autoantibody that binds to the thyroid-stimulating hormone receptor (TSHR) on thyroid cells and mimics the effect of TSH itself. This binding leads to continuous and unregulated production of thyroid hormones—primarily T3 and T4—regardless of the body’s actual need. TSI is not merely a marker of disease; it is the underlying cause of hyperthyroidism in Graves’ disease.

Under normal conditions, the pituitary gland regulates thyroid hormone output by adjusting levels of TSH in response to circulating thyroid hormone levels—an elegant negative feedback loop. TSI short-circuits this system. Even if the body has sufficient or excess thyroid hormone, TSI keeps the thyroid gland in overdrive, leading to symptoms like weight loss, heat intolerance, tremor, and anxiety. Over time, this unchecked activity can affect multiple organ systems, including the heart, bones, and brain.

TSI is a subset of TSH receptor antibodies (TRAb), but not all TRAbs are the same. Some TRAbs stimulate (TSI), some block, and others are neutral. What sets TSI apart is its functional activity: it stimulates thyroid hormone production. Modern assays can now distinguish TSI from blocking or neutral antibodies, making the test more informative than a general TRAb assay in specific contexts.

TSI has strong diagnostic value. Nearly all patients with untreated Graves’ disease will test positive. Third-generation TSI bioassays, which measure the antibody’s ability to increase cAMP production in thyroid cells, are particularly sensitive and specific. In fact, in overt cases of hyperthyroidism, the presence of TSI is nearly synonymous with Graves’ disease.

It’s also prognostic. High TSI levels at diagnosis correlate with a longer course of illness, greater severity, and higher risk of relapse after stopping anti-thyroid medications. Patients with persistently elevated TSI after treatment are more likely to experience a recurrence of symptoms, whereas declining or undetectable TSI levels suggest remission.

TSI also plays a key role outside the thyroid gland. In Graves’ orbitopathy (also called thyroid eye disease), TSI interacts with TSH receptors in orbital tissues, contributing to inflammation, swelling, and remodeling around the eyes. Higher TSI concentrations tend to predict more active and severe eye involvement, and they may help forecast which patients are less likely to respond to immunosuppressive therapy.

During pregnancy, TSI can cross the placenta and stimulate the fetal thyroid, leading to fetal or neonatal hyperthyroidism—a rare but serious complication. This is especially relevant in women with a history of Graves’ disease who have undergone definitive treatment (like radioactive iodine or surgery) but still have circulating TSI. For this reason, TSI testing is recommended between 24 and 28 weeks of gestation in these patients. A high TSI level may warrant closer fetal monitoring and even intervention.

Compared to general TRAb testing, TSI assays offer a more precise view into the biology of Graves’ disease and its complications. While TRAb tests can detect both stimulating and blocking antibodies, only TSI confirms active stimulation of the thyroid. In certain clinical situations—especially pregnancy, orbitopathy, or ambiguous hyperthyroidism—TSI gives the clearest signal about what’s happening and what to expect next.

During pregnancy, TSI can cross the placenta and stimulate the fetal thyroid, leading to fetal or neonatal hyperthyroidism—a rare but serious complication. This is especially relevant in women with a history of Graves’ disease who have undergone definitive treatment (like radioactive iodine or surgery) but still have circulating TSI. For this reason, TSI testing is recommended between 24 and 28 weeks of gestation in these patients. A high TSI level may warrant closer fetal monitoring and even intervention.

Compared to general TRAb testing, TSI assays offer a more precise view into the biology of Graves’ disease and its complications. While TRAb tests can detect both stimulating and blocking antibodies, only TSI confirms active stimulation of the thyroid. In certain clinical situations—especially pregnancy, orbitopathy, or ambiguous hyperthyroidism—TSI gives the clearest signal about what’s happening and what to expect next.