At what levels of Thyroid-Stimulating Hormone (TSH), free Thyroxine (T4), and free Triiodothyronine (T3) should antithyroid drugs be initiated for patients with symptomatic hyperthyroidism?

Antithyroid Drug Initiation Thresholds

Antithyroid drugs should be initiated when TSH is suppressed (<0.1 mIU/L) AND free T4 and/or free T3 are elevated above the reference range, confirming overt hyperthyroidism. 1

Diagnostic Confirmation Required Before Treatment

• Measure TSH, free T4, and free T3 simultaneously to establish the diagnosis of overt hyperthyroidism, as TSH suppression alone is insufficient 1
• Confirm TSH <0.1 mIU/L with elevated free T4 (above laboratory reference range, typically >19-25 pmol/L) and/or elevated free T3 (above reference range) 1, 2
• Do not initiate antithyroid drugs based on suppressed TSH with normal thyroid hormones (subclinical hyperthyroidism), as this condition is typically managed with observation or definitive therapy rather than antithyroid medications 1

Specific Hormone Level Thresholds

• Overt hyperthyroidism requiring antithyroid drugs is defined as TSH <0.1 mIU/L with free T4 elevated above the upper limit of normal 1
• T3 thyrotoxicosis (isolated T3 elevation) occurs when TSH is suppressed (<0.1 mIU/L), free T4 is normal or low, but free T3 is elevated above the reference range 2, 3
• The likelihood of detecting clinically significant T3 thyrotoxicosis increases substantially when TSH <0.01 μIU/mL rather than just <0.3 μIU/mL 3

T3 Thyrotoxicosis Considerations

• Measure free T3 specifically when TSH <0.01 mIU/L and free T4 is normal or decreased, as this pattern suggests T3 thyrotoxicosis requiring antithyroid drug therapy 3
• T3 thyrotoxicosis represents true hyperthyroidism requiring treatment, not subclinical disease, despite normal T4 levels 2
• In untreated hyperthyroidism, the T4/T3 ratio by weight averages 48 (compared to 71 in euthyroid patients), indicating relative T3 overproduction 4

Subclinical Hyperthyroidism Management

• Subclinical hyperthyroidism (TSH <0.1 mIU/L with normal free T4 and T3) does not typically warrant antithyroid drug initiation 1
• Treatment for subclinical hyperthyroidism is reserved for patients >65 years or those with persistent TSH <0.1 mIU/L who are at high risk for osteoporosis and cardiovascular disease 1
• Definitive therapy (radioactive iodine or surgery) is preferred over antithyroid drugs for subclinical hyperthyroidism when treatment is indicated 1

Critical Pitfalls to Avoid

• Never start antithyroid drugs based solely on suppressed TSH without confirming elevated free T4 and/or free T3, as suppressed TSH can occur with subclinical hyperthyroidism, nonthyroidal illness, or medication effects 1, 3
• Do not miss T3 thyrotoxicosis by failing to measure free T3 when TSH is profoundly suppressed (<0.01 mIU/L) but free T4 is normal 3
• Confirm the diagnosis with repeat testing before initiating antithyroid drugs, as transient TSH suppression can occur with various conditions 5

Treatment Selection After Diagnosis

• First-line treatment options for confirmed overt hyperthyroidism include antithyroid drugs (methimazole or propylthiouracil), radioactive iodine ablation, or surgery 1
• Propylthiouracil causes greater acute decreases in serum T3 compared to methimazole due to inhibition of peripheral T4-to-T3 conversion, which may be advantageous in severe thyrotoxicosis 4
• Treatment choices should be individualized based on etiology (Graves disease vs toxic nodules), patient age, symptom severity, and patient preference 1