What is the treatment for thyroid peroxidase (TPO) deficiency?

Treatment for Thyroid Peroxidase (TPO) Deficiency

Thyroid peroxidase (TPO) deficiency is treated with levothyroxine replacement therapy, which should be initiated when TSH levels are elevated or when patients are symptomatic, even with subclinical hypothyroidism when TSH is >10 mIU/L or when TPO antibodies are elevated. 1, 2

Diagnosis and Evaluation

• Thyroid peroxidase (TPO) is a key enzyme in thyroid hormone formation and a major autoantigen in autoimmune thyroid diseases 3
• Diagnosis is based on blood levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) 2
• If TSH is abnormal, free T4 and, if indicated, total T3 should be measured 1
• The presence of thyroid autoantibodies (anti-TPO and anti-thyroglobulin) identifies patients at increased risk for thyroid autoimmunity 1
• Even within the normal TSH range, TPO antibody titers correlate with TSH levels, suggesting impending thyroid failure 3

Treatment Algorithm

Initial Treatment

• Start levothyroxine at 1.5 to 1.8 mcg per kg per day in most adult patients 2
• For patients over 60 years or with known/suspected ischemic heart disease, start at a lower dosage (12.5 to 50 mcg per day) 2
• For pediatric patients at risk for hyperactivity, start at one-fourth the recommended full replacement dosage and increase on a weekly basis by one-fourth until the full recommended dosage is reached 4

Dosage Adjustment

• Monitor serum TSH levels 6-8 weeks after any dosage change in adults 4
• In pediatric patients, monitor TSH and total or free-T4 at 2 and 4 weeks after treatment initiation, 2 weeks after any dosage change, and then every 3-12 months thereafter 4
• Adjust dosage to maintain TSH within the normal reference range 4

Special Populations

• Pregnant patients with pre-existing hypothyroidism should increase their weekly dosage by 30% (take one extra dose twice per week) 2
• For new onset hypothyroidism during pregnancy with TSH ≥10 IU/L, start at 1.6 mcg/kg/day 4
• For new onset hypothyroidism during pregnancy with TSH <10 IU/L, start at 1.0 mcg/kg/day 4

Monitoring and Follow-up

• For adults on stable replacement dosage, evaluate clinical and biochemical response every 6-12 months 4
• Persistent clinical and laboratory evidence of hypothyroidism despite adequate replacement may indicate inadequate absorption, poor compliance, or drug interactions 4
• Long-term follow-up studies show that TPO antibody levels decline in most patients with Hashimoto's thyroiditis taking levothyroxine, with a mean decrease of 45% after 1 year and 70% after 5 years 5
• However, TPO antibody levels become negative in only a minority of patients (approximately 16%) even after long-term treatment 5

Clinical Considerations and Pitfalls

• Subclinical hypothyroidism should be treated when TSH >10 mIU/L or when TPO antibodies are elevated 2
• Avoid overtreatment as it may have negative effects on cardiovascular function, bone metabolism, and cognitive function 4
• In pediatric patients, undertreatment may adversely affect cognitive development and linear growth, while overtreatment is associated with craniosynostosis and acceleration of bone age 4
• Adding triiodothyronine (T3) is not recommended, even in patients with persistent symptoms and normal TSH levels 2
• Rule out adrenal insufficiency before initiating thyroid hormone replacement, as levothyroxine is contraindicated in uncorrected adrenal insufficiency 4, 6

By following this treatment approach, most patients with TPO deficiency will achieve symptom relief and normalized thyroid function, although careful monitoring and dosage adjustment are essential for optimal outcomes.