What to do with a patient on Tecentriq (atezolizumab) and Avastin (bevacizumab) with a history of hypothyroidism, on levothyroxine, who has a suppressed Thyroid-Stimulating Hormone (TSH) level?

Management of Suppressed TSH in a Patient on Levothyroxine with Immune Checkpoint Inhibitor Therapy

The levothyroxine dose should be reduced by 25 mcg in this patient with a suppressed TSH (0.12) but normal free T4 and T3 levels while on immunotherapy.

Assessment of Current Thyroid Status

• TSH of 0.12 with normal free T4 and T3 indicates subclinical hyperthyroidism
• This patient has two important clinical contexts:
  1. History of hypothyroidism on levothyroxine replacement
  2. Currently receiving immunotherapy (Tecentriq/atezolizumab and Avastin/bevacizumab)

Clinical Decision Algorithm

Step 1: Determine if TSH suppression is appropriate

• For patients with thyroid cancer requiring TSH suppression, maintaining TSH below 0.1 mIU/L may be appropriate for those with known residual disease or high risk of recurrence 1
• However, this patient has a history of hypothyroidism, not thyroid cancer
• For patients with primary hypothyroidism, the goal is to maintain TSH within the normal reference range (typically 0.5-4.5 mIU/L) 2

Step 2: Evaluate risks of continued TSH suppression

• Approximately 25% of patients on levothyroxine are inadvertently maintained on doses high enough to suppress TSH 2
• Risks of chronic TSH suppression include:
  • Adverse effects on bone mineral density
  • Increased risk of atrial fibrillation
  • Cardiovascular complications, especially in elderly patients 2

Step 3: Consider impact of immunotherapy

• Immune checkpoint inhibitors like Tecentriq (atezolizumab) can cause thyroid dysfunction
• Common side effect with some immunotherapies is increased serum TSH due to interference in thyroid hormone metabolism 1
• However, in this case, TSH is suppressed rather than elevated, suggesting overtreatment with levothyroxine rather than an immune-related adverse event

Management Plan

1. Reduce levothyroxine dose by 25 mcg

   • For patients with suppressed TSH (<0.1 mIU/L), dose reduction is recommended 2, 3
   • A 25 mcg reduction is appropriate when the original dose is 175 mcg or less, as it is less likely to result in an elevated TSH (3.8% vs 10.0% with 50 mcg reduction) 3

2. Follow-up monitoring

   • Recheck thyroid function tests in 6-8 weeks 2
   • This timing allows for the long half-life of levothyroxine and establishment of new steady state

3. Continued surveillance

   • Monitor TSH every 4-6 weeks as part of routine clinical monitoring for patients on immune checkpoint inhibitor therapy 1
   • Watch for potential development of immune-related thyroiditis, which can cause transient hyperthyroidism followed by hypothyroidism

Important Considerations

• Development of a low TSH on therapy suggests either overtreatment or recovery of thyroid function 1
• Immunotherapy can be continued while adjusting the levothyroxine dose, as this is not an immune-related adverse event requiring treatment interruption
• If TSH remains suppressed despite dose reduction, consider further dose adjustment
• If symptoms of hyperthyroidism develop (tachycardia, tremor, sweating), more aggressive dose reduction may be needed

Pitfalls to Avoid

• Don't attribute all thyroid abnormalities in patients on immunotherapy to immune-related adverse events; this patient's suppressed TSH is more likely due to excessive levothyroxine dosing
• Don't reduce the dose too aggressively, as this could lead to hypothyroidism symptoms
• Don't ignore the suppressed TSH, as chronic subclinical hyperthyroidism carries long-term health risks