Immunotherapy side effect- Thyroid function

 Thyroid problems

Hypothyroidism 20-40% of patients can be affected. Watch for onset even after completion of IO treatment.

Nivo ( 3%) ipi (8%). Combination = 13% ie there is a synergism.

Suboptimal thyroid function at baseline can be a negative OS predictor unless corrected.

1.  We often see a high TSH suggestive of hypothyroidism. Treat with L-thyroxine if:

- TSH > 10 without symptoms or

-TSH high and FT4 low or with symptoms

2. When is TSH  the first clue that the patient is developing hypopituitarism?

-when TSH is low ( because it comes from the pituitary) and the FT 4 is low

- if the FT4 is low, and TSH is normal, recheck next cycle. Also check 8 am cortisol to screen for hypopituitarism.

3. What about hyperthyroidism/ thyroiditis related to immunotherapy?

-the severity of clinical manifestations often does not correlate with elevation of FT3 or FT4

-why do an anti TPO Ab: it is positive in Grave's disease, but not with hyperfunctioning adenoma or multinodular goiter. Not positive in IO thyroiditis.

-anti TPO Ab can be seen in 10-12% of healthy population. Other relevant antibodies- anti thyroid receptor

- in elderly, with low TSH, always look for Afib ( get EKG, clinically assess cardiac function)

-A radioactive uptake scan shows low uptake in IO thyroiditis in contrast to high uptake with a PET scan. ( remember autoimmune ie Grave's disease shows high RAI uptake)

4. Who is more likely to develop thyroid dysfunction?

- smokers, family hx of autoimmune disorders, hypertension

5. How often to screen?

every 3 week cycle or monthly for the first 3 months, then every other cycle. Typically seen after 6 weeks.

6. Blood tests and PET scan in detection of irAE

- PET may pick up colitis ( 28%), thyroiditis 13%, myositis 13%, pneumonitis ( 6.5%), hepatitis (6.5%) hypophysitis 4.3% ( Reference)

-CD4/CD8 ratio falls before the onset of ir AE due to expansion of CD 8 cells (Reference)

7. Treatment of hyperthyroidism:

if subclinical hyperthyroidism ie detectable but low TSH, normal FT4, observe, recheck

if neck pain--> NSAID, steroids, US thyroid, EKG and cardiac eval in elderly, am cortisol

betablockers, propranolol. Monitor for high TSH and replace L-thyroxine.