Thyroid Dysfunction from Immunotherapy: Detection and Management

Thyroid dysfunction is one of the most common endocrine side effects of checkpoint inhibitors, affecting 5-10% of patients on single-agent therapy and up to 15-20% with combination immunotherapy. Fortunately, it's usually manageable with simple hormone replacement.

**Types of Thyroid Dysfunction**

Primary Hypothyroidism (Most Common):
- Underactive thyroid gland
- Occurs in 5-10% of patients
- Usually permanent, requires lifelong replacement
- Can develop months after starting treatment

Thyroiditis (Transient):
- Initial hyperthyroidism followed by hypothyroidism
- Self-limited inflammation
- May or may not require treatment
- More common with PD-1 inhibitors

Hyperthyroidism (Rare):
- Overactive thyroid
- Usually temporary
- Affects <2% of patients
- May precede hypothyroidism

**Symptoms to Watch For**

Hypothyroidism (Underactive):
- Fatigue and weakness
- Weight gain
- Cold intolerance
- Constipation
- Dry skin and hair
- Depression or mood changes
- Slowed thinking, poor concentration
- Hoarse voice
- Muscle aches

Hyperthyroidism (Overactive):
- Rapid heartbeat or palpitations
- Weight loss despite normal appetite
- Heat intolerance, excessive sweating
- Tremor
- Anxiety, irritability
- Insomnia
- Frequent bowel movements
- Muscle weakness

Thyroiditis (Inflammation):
- Neck pain or tenderness
- Difficulty swallowing
- Initial hyperthyroid symptoms
- Followed by hypothyroid symptoms weeks later

**Screening and Diagnosis**

Baseline Testing (Before Starting Immunotherapy):
- TSH (thyroid stimulating hormone)
- Free T4 (thyroxine)
- Free T3 if abnormal results
- TPO antibodies (optional)

Regular Monitoring During Treatment:
- TSH and Free T4 before each infusion initially
- Then every 6-12 weeks if stable
- More frequent if symptoms develop

Diagnostic Findings:

Primary Hypothyroidism:
- Elevated TSH (>10 mIU/L)
- Low Free T4

Subclinical Hypothyroidism:
- Mildly elevated TSH (4.5-10 mIU/L)
- Normal Free T4

Hyperthyroidism:
- Low TSH (<0.1 mIU/L)
- Elevated Free T4 and/or Free T3

Thyroiditis:
- Fluctuating thyroid values
- May see brief hyperthyroid phase
- ESR/CRP may be elevated

**Treatment Approaches**

Overt Hypothyroidism:
- Start levothyroxine (Synthroid) replacement
- Initial dose: 1.6 mcg/kg body weight daily
- Take on empty stomach in morning
- Typical doses: 75-150 mcg daily
- Check TSH/Free T4 every 6-8 weeks until stable
- Adjust dose to maintain TSH 0.5-2.5 mIU/L
- Continue immunotherapy - no need to hold treatment
- Lifetime treatment usually required

Subclinical Hypothyroidism:
- If TSH 7-10: Consider treatment if symptomatic
- If TSH >10: Start levothyroxine
- Monitor closely, may progress to overt hypothyroidism

Hyperthyroidism (Mild):
- Beta-blockers for symptom control (propranolol)
- No antithyroid drugs usually needed
- Often resolves spontaneously in 4-8 weeks
- Monitor closely for progression to hypothyroidism

Severe Hyperthyroidism:
- May require antithyroid medications temporarily
- Propranolol for heart rate and symptoms
- Endocrinology consultation recommended
- Rare with checkpoint inhibitors

Thyroiditis:
- NSAIDs or steroids for pain and inflammation
- Beta-blockers if hyperthyroid symptoms
- Watch for subsequent hypothyroidism
- May need levothyroxine long-term

**Managing Levothyroxine Therapy**

Taking Your Medication:
- Take on empty stomach
- 30-60 minutes before breakfast
- At least 4 hours separate from:
* Calcium supplements
* Iron supplements
* Antacids
* Coffee (may reduce absorption)
- Be consistent with timing
- Don't skip doses

Monitoring:
- Check TSH/Free T4 6-8 weeks after any dose change
- Once stable, check every 6-12 months
- More frequent monitoring if:
* Dose adjustments
* New medications
* Weight change >10%
* Pregnancy

Signs of Correct Dosing:
- TSH 0.5-2.5 mIU/L (optimal)
- Symptoms resolved
- Normal energy levels
- Stable weight

Signs of Under-Replacement:
- TSH >4.0 mIU/L
- Persistent fatigue
- Weight gain
- Cold intolerance

Signs of Over-Replacement:
- TSH <0.1 mIU/L
- Palpitations
- Anxiety
- Weight loss
- Insomnia

**Impact on Cancer Treatment**

Can I Continue Immunotherapy?
- YES! Thyroid dysfunction rarely requires stopping treatment
- Start levothyroxine and continue checkpoint inhibitors
- No dose adjustments of immunotherapy needed
- Thyroid dysfunction is not a reason to discontinue cancer therapy

Does Thyroid Treatment Affect Cancer Outcomes?
- No evidence that thyroid replacement interferes with immunotherapy
- Some studies suggest patients who develop thyroid issues may have better cancer outcomes
- Possible indicator of robust immune activation

**Long-Term Management**

Permanent vs. Temporary:
- Most immune-related hypothyroidism is permanent
- Continue levothyroxine indefinitely
- Periodic trials off medication rarely successful
- Hyperthyroidism usually temporary

Follow-Up Care:
- Annual TSH monitoring minimum
- Dose adjustments as needed
- Watch for symptoms despite normal TSH
- Consider changing to different levothyroxine preparation if not feeling well on treatment

Lifestyle Considerations:
- Maintain consistent sleep schedule
- Regular exercise helps energy levels
- Balanced diet supports thyroid function
- Manage stress
- Adequate iodine intake (but don't oversupplement)

**Special Situations**

Weight Changes:
- May need dose adjustment if gain/lose >10% body weight
- Recheck TSH 6-8 weeks after weight change

Pregnancy:
- Increase levothyroxine 30-50% immediately upon confirmation
- Check TSH every 4 weeks
- Critical for fetal development

Aging:
- May need lower doses as metabolism slows
- Monitor for overtreatment symptoms
- Adjust carefully in elderly patients

**Questions to Ask Your Doctor**

- What are my baseline thyroid levels?
- How often will you check my thyroid function?
- What symptoms should I report?
- If I need thyroid replacement, will I take it forever?
- Will thyroid problems affect my cancer treatment?
- Do I need to see an endocrinologist?

**Patient Success Story**

"After 4 months of Keytruda, I felt exhausted all the time - even worse than my usual cancer fatigue. My oncologist checked my thyroid and found my TSH was 18 (severely elevated). I started levothyroxine 100 mcg, and within 3 weeks, my energy improved dramatically. I've been on the same dose for a year now, feel great, and my cancer is responding well. It's a simple pill once a day - totally manageable."

Our team can help you understand and manage endocrine side effects throughout your immunotherapy journey.