Immunotherapy harnesses the body’s immune system to fight cancer, but these treatments can cause side effects called immune-related adverse events. The thyroid gland is a commonly affected organ, leading to changes in its function and raising questions about recovery.
How Immunotherapy Affects the Thyroid
Immune checkpoint inhibitors (ICIs) are a class of immunotherapy that work by “releasing the brakes” on the immune system, allowing T-cells to better recognize and attack cancer cells. This enhanced immune activity can sometimes mistakenly target healthy tissues, including the thyroid gland. The resulting inflammation of the thyroid is termed thyroiditis. This process involves a complex interplay of immune cells and their signaling molecules, leading to the destruction of thyroid cells.
The incidence of thyroiditis in patients treated with ICIs ranges from 10% to 20%. These changes typically occur early in treatment, with dysfunction appearing around 2.8 months. The immune system’s activation can lead to a loss of tolerance towards its own tissues.
Types of Thyroid Dysfunction After Immunotherapy
The thyroid dysfunction observed after immunotherapy often follows a distinct pattern. Patients frequently experience an initial phase of hyperthyroidism, also known as thyrotoxicosis. This occurs as the inflamed thyroid gland releases pre-formed thyroid hormones into the bloodstream due to cell destruction. This hyperthyroid phase is generally transient and may be asymptomatic or cause mild symptoms.
Following this initial phase, many patients transition to hypothyroidism, where the thyroid gland becomes underactive. This occurs because the initial inflammation damages enough thyroid tissue to impair its ability to produce sufficient hormones. The shift from hyperthyroidism to hypothyroidism can be rapid, often occurring within 3 months. In some instances, patients may present directly with hypothyroidism without a noticeable hyperthyroid phase.
Factors Influencing Thyroid Recovery
The question of whether thyroid function recovers after immunotherapy is complex. While some cases of immunotherapy-induced thyroid dysfunction can be transient, particularly the initial hyperthyroid phase, full recovery to normal thyroid function is uncommon. The majority of patients who develop hypothyroidism will require long-term thyroid hormone replacement therapy.
Several factors influence thyroid recovery and the type of dysfunction. The specific immune checkpoint inhibitor used plays a role; anti-PD-1 and anti-PD-L1 agents are more frequently associated with thyroid dysfunction than anti-CTLA-4 monotherapy. Combination immunotherapy regimens often carry a higher risk of thyroid-related adverse events. Pre-existing thyroid conditions or certain baseline antibody levels can also increase the risk.
Monitoring and Management of Thyroid Changes
Regular monitoring of thyroid function is important for patients undergoing immunotherapy. Thyroid-stimulating hormone (TSH) and free thyroxine (free T4) levels are typically checked at baseline before treatment and then periodically, often every 4 to 6 weeks, during and after therapy. This routine testing helps detect changes early, even before symptoms appear.
For the transient hyperthyroid phase, management usually involves symptomatic treatment, such as beta-blockers to control heart rate, without the need for thyroid-suppressing medications. If hypothyroidism develops, the standard approach is thyroid hormone replacement therapy, most commonly with levothyroxine. This medication replaces the hormones the thyroid gland can no longer produce. Immunotherapy can typically be continued while thyroid dysfunction is managed with hormone replacement.