What is the initial step in the workup of a patient with a low Thyroid-Stimulating Hormone (TSH) level?

Initial Workup for Low TSH

When a patient presents with a low TSH level, the first step in the workup should be to measure free T4 (FT4) and free T3 (FT3) levels to determine the cause and severity of potential thyroid dysfunction. 1

Diagnostic Algorithm for Low TSH

1. Measure Free T4 and Free T3 levels

   • Free hormone measurements are more reliable than total hormone levels as they represent the biologically active hormone fraction 2
   • Free T4 is particularly important as it's often elevated in cases of suppressed TSH, even when total T4 appears normal 3

2. Interpret the pattern of results:

   • Low TSH + High FT4/FT3: Overt hyperthyroidism
   • Low TSH + Normal FT4/FT3: Subclinical hyperthyroidism (though free T4 may be in the upper normal range) 3
   • Low TSH + Low/Normal FT4/FT3: Consider central hypothyroidism (pituitary or hypothalamic disorder) 1

3. Consider common causes based on pattern:

   • Iatrogenic (excessive levothyroxine treatment)
   • Graves' disease
   • Toxic multinodular goiter
   • Thyroiditis
   • Pituitary or hypothalamic disorders

Important Considerations

Potential Interference in Laboratory Testing

Be aware of factors that can affect thyroid test interpretation:

• Heterophile antibodies can cause falsely low TSH readings 4, 5
• Thyroid hormone autoantibodies may interfere with FT4/FT3 measurements 5
• Abnormal albumin variants can affect free hormone measurements 5

Special Populations

• Elderly patients: More susceptible to adverse effects of thyroid hormone excess; require more conservative management 1
• Patients with thyroid cancer: May have intentionally suppressed TSH; consult with treating endocrinologist before making changes 1
• Pregnancy: Requires trimester-specific reference ranges 1

Follow-up Testing

If iatrogenic subclinical hyperthyroidism is confirmed:

• Consider levothyroxine dose reduction (typically 20% from initial dose) 1
• Recheck thyroid function tests in 4-6 weeks 1
• Monitor more frequently in elderly patients or those with cardiac disease 1

Common Pitfalls to Avoid

1. Misinterpreting normal total T4/T3 with low TSH: Even with normal total hormone levels, free T4 is often elevated when TSH is suppressed 3

2. Overlooking central hypothyroidism: Low TSH with low/normal free hormone levels may indicate pituitary or hypothalamic disorders 1

3. Ignoring laboratory interferences: Discrepancies between clinical presentation and laboratory values should prompt consideration of assay interference 4, 5

4. Failing to consider medication effects: Many medications can affect thyroid function tests or thyroid hormone metabolism

5. Overlooking non-thyroidal illness: Severe illness can alter thyroid function tests without true thyroid dysfunction

Remember that free hormone measurements are more reliable than total hormone measurements for assessing thyroid function, especially when TSH levels are abnormal 2.