[Thyroid dysfunctions secondary to cancer immunotherapy]

Area of Science:

• Endocrinology
• Oncology
• Immunology

Background:

• Immune checkpoint inhibitors (CPI), including anti-PD(L)1 and anti-CTLA4 therapies, have significantly improved patient outcomes in various cancers.
• Thyroid disorders represent the most common endocrine adverse events associated with CPI treatment, observed in both clinical trials and routine practice.
• The incidence of CPI-induced thyroid dysfunction varies depending on the specific agent used, with higher rates reported for anti-programmed cell death 1 (PD1) and anti-programmed cell death-ligand 1 (PDL1) therapies.

Purpose of the Study:

• To summarize the clinical presentation, diagnosis, and management of thyroid dysfunction secondary to immune checkpoint inhibitor therapy.
• To emphasize the high frequency of thyroid disorders as an endocrine side effect of CPI.
• To highlight the importance of monitoring thyroid function during CPI treatment.

Main Methods:

• Review of clinical trial data and routine clinical practice observations regarding CPI-induced thyroid disorders.
• Analysis of the incidence, timing, clinical symptoms, and diagnostic criteria for these thyroid dysfunctions.
• Evaluation of management strategies, including symptomatic treatment and hormone replacement therapy.

Main Results:

• Thyroid dysfunction typically manifests 2 to 4 cycles after CPI initiation, often as painless thyroiditis with a biphasic course: initial thyrotoxicosis followed by secondary, frequently permanent, hypothyroidism.
• Clinical symptoms are often nonspecific, such as asthenia and weight changes, with occasional cardiac rhythm disturbances.
• Diagnosis relies on thyroid function tests (TSH and FT4), with further investigations usually unnecessary.

Conclusions:

• CPI-induced thyroid dysfunction is a common complication requiring vigilant monitoring.
• Management involves symptomatic treatment for thyrotoxicosis (e.g., beta-blockers) and prompt thyroid hormone replacement for hypothyroidism.
• Thyroid dysfunction does not necessitate the discontinuation of immunotherapy, underscoring the need for continued monitoring and management.