How should hypothyroidism be monitored and managed in the setting of ICPI therapy?
Monitoring for and treatment of these toxicities is critically important. The American Society of Clinical Oncology (ASCO) recommends measuring serum TSH and free T 4 levels every 4 to 6 weeks as part of routine clinical monitoring or for case detection in symptomatic patients on therapy. For primary hypothyroidism, grade 1 toxicity is a serum TSH level that becomes mildly elevated but is < 10 mIU/L in an asymptomatic patient; in this situation, it is recommended that ICPI therapy be continued, with close monitoring of both TSH and free T 4 . Grade 2 toxicity is when the serum TSH level is persistently > 10 mIU/L and moderate symptoms are present but the patient can still perform ADLs. In this scenario, thyroid hormone replacement should be prescribed, and ICPI therapy may need to be held temporarily until symptoms improve; TSH should be monitored every 6 to 8 weeks while titrating hormone replacement (alternatively, free T 4 can be checked up to every 2 weeks to titrate hormone replacement if the free T 4 was initially low). Grade 3 or 4 toxicity is defined as severe hypothyroid symptoms with medically significant or life-threatening consequences that prevent a patient from performing ADLs. ICPI therapy should be withheld in such cases until symptoms resolve with thyroid hormone replacement; the patient should be admitted to the hospital and given intravenous (IV) thyroid hormone replacement if signs of myxedema coma (decompensated hypothyroidism) are present (i.e., hypothermia, bradycardia). Prior to initiation of thyroid medication, all patients should have their adrenal axis evaluated to rule out the presence of adrenal insufficiency that maybe exacerbated if untreated prior to the initiation of thyroid hormone therapy.