From the Guidelines
TSH receptor antibody testing should be considered if there are clinical features and suspicion of Graves’ disease, such as ophthalmopathy and T3 toxicosis, as recommended in the 2021 ASCO guideline update 1. When evaluating patients with suspected thyroid dysfunction, particularly those on immune checkpoint inhibitor (ICPi) therapy, it is essential to consider the role of TSH receptor antibodies.
- These antibodies can stimulate the thyroid gland, leading to hyperthyroidism, or block the thyroid-stimulating hormone (TSH) receptor, resulting in hypothyroidism.
- The 2021 ASCO guideline update suggests checking TSH every 4-6 weeks as part of routine clinical monitoring for asymptomatic patients on ICPi therapy 1.
- For symptomatic patients, TSH and free thyroxine (FT4) should be used for case detection, and triiodothyronine (T3) can be helpful in highly symptomatic patients with minimal FT4 elevations 1.
- Low TSH with a low FT4 is consistent with central hypothyroidism, and evaluation should be performed as per hypophysitis, as outlined in the guideline 1. Key considerations in the management of thyroid dysfunction in patients on ICPi therapy include:
- Grading of symptoms, with Grade 1 being asymptomatic or mild symptoms, Grade 2 being moderate symptoms, and Grade 3-4 being severe symptoms or life-threatening consequences 1.
- Management strategies, such as continuing ICPi, holding ICPi, or referring to endocrinology for additional workup and possible medical thyroid suppression, depend on the severity of symptoms and the presence of TSH receptor antibodies 1.
From the Research
TSH Receptor Antibodies
- TSH receptor antibodies play a key role in the pathogenesis of Graves' disease, and their levels correlate with the clinical course 2.
- The levels of TSH receptor antibodies can be used to predict the risk of relapse in patients with Graves' disease, with higher levels indicating a greater risk of relapse 2, 3.
- Antithyroid drug therapy can decrease the production of TSH receptor antibodies, and the addition of thyroxine to antithyroid drug treatment may also decrease the levels of these antibodies 4, 5.
- Therapeutic plasma exchange can be used to clear TSH receptor antibodies from the blood, resulting in a pre-surgical euthyroid state without antithyroid drug therapy 6.
Measurement and Prognosis
- The measurement of TSH receptor antibody levels can be used to confirm the diagnosis of Graves' disease, with high sensitivity and specificity 3.
- TSH receptor antibody levels can also be used to predict the duration of remission in patients with Graves' disease, with lower levels indicating a longer remission duration 3.
- Elevated TSH receptor antibody levels are associated with an increased risk of fetal and neonatal thyrotoxicosis in pregnant women with current or previously treated Graves' disease 2.
Treatment Implications
- Elevated TSH receptor antibody levels may favor definitive treatment in the form of radioactive iodine or thyroidectomy, depending on the presence or absence of moderate-to-severe Graves' ophthalmopathy and the ability to comply with radiation protection requirements 2.
- The use of antithyroid drugs in early pregnancy is associated with an increased risk of congenital anomalies, and early ablative treatment may be considered in women of childbearing age at higher risk of relapse of Graves' disease 2.