What dose of Synthroid (levothyroxine) should be started in a patient with metastatic prostate cancer, on lifelong Elagolix (Elagard) and Apalutamide, post radiation therapy, with a Thyroid Stimulating Hormone (TSH) level of 13.10 mIU/L and a weight of 62 kg?

Levothyroxine Dosing for Hypothyroidism in Metastatic Prostate Cancer Patient on Apalutamide

For a 62 kg patient with metastatic prostate cancer on lifelong Eligard and apalutamide with TSH of 13.10 mIU/L, start levothyroxine at 75-88 mcg daily.

Understanding the Clinical Situation

This patient presents with:

• Metastatic prostate cancer
• Current treatment with Eligard (leuprolide acetate) and apalutamide
• History of radiation therapy
• Elevated TSH (13.10 mIU/L) indicating hypothyroidism
• Weight of 62 kg

Apalutamide-Induced Hypothyroidism

Apalutamide is known to cause thyroid dysfunction as a common adverse effect:

• Hypothyroidism occurs in approximately 8.1% of patients on apalutamide 1
• Thyroid dysfunction typically develops within a median of 19 weeks after starting apalutamide, but can occur as early as 2-4 weeks 2
• Patients may develop either new hypothyroidism or worsening of pre-existing hypothyroidism 2

Levothyroxine Dosing Considerations

Initial Dosing Algorithm:

1. Standard weight-based dosing: 1.6 mcg/kg/day

   • For 62 kg patient: 1.6 × 62 = 99.2 mcg/day

2. Adjustment factors:

   • Patient has metastatic cancer: Consider starting at lower dose
   • No apparent cardiac disease mentioned: No additional reduction needed
   • TSH is moderately elevated at 13.10 mIU/L: Requires full replacement

3. Recommended starting dose:

   • 75-88 mcg daily (approximately 75-90% of full calculated dose)
   • Start with 75 mcg daily if concerned about age-related factors
   • Use 88 mcg daily if more rapid normalization is desired

Monitoring Protocol:

• Check TSH and free T4 in 4-6 weeks after initiation
• Adjust dose in 12-25 mcg increments based on TSH response
• Once stable, monitor every 3 months while on apalutamide 2
• Be prepared to increase dose 2-3 fold from baseline while patient remains on apalutamide 2

Special Considerations for This Patient

1. Metastatic prostate cancer management:

   • TSH suppression is not the goal (unlike in thyroid cancer)
   • Target TSH should be within normal range (0.5-4.0 mIU/L)

2. Apalutamide effect on thyroid function:

   • Patients on apalutamide often require higher levothyroxine doses 2
   • Monitor closely as dose requirements may increase over time
   • Be prepared for dose reduction if apalutamide is discontinued (thyroid function typically normalizes within 11 weeks after stopping apalutamide) 2

3. Post-radiation considerations:

   • Radiation therapy may affect thyroid function if neck was in radiation field
   • This may contribute to hypothyroidism in addition to apalutamide effect

Pitfalls to Avoid

1. Underdosing: Starting with too low a dose may delay symptom improvement
2. Overdosing: Starting with full calculated dose may cause thyrotoxic symptoms
3. Inadequate monitoring: Failure to check thyroid function regularly while on apalutamide
4. Missing dose adjustments: Failing to increase dose as needed while continuing apalutamide
5. Medication interactions: Ensure proper absorption by taking levothyroxine on empty stomach, separated from other medications

Follow-up Plan

• Recheck TSH and free T4 in 4-6 weeks
• Adjust dose as needed to normalize TSH
• Continue monitoring every 3 months while on apalutamide
• If apalutamide is discontinued, recheck thyroid function 2-3 months after stopping and adjust levothyroxine dose accordingly