Laboratory Evaluation for Low TSH
For patients with a low TSH level, a comprehensive thyroid panel including free T4, free T3, and thyroid antibody testing should be ordered to determine the underlying cause and guide appropriate management.
Initial Evaluation for Low TSH
- Free T4 (FT4) should be measured to differentiate between subclinical hyperthyroidism (normal FT4) and overt hyperthyroidism (elevated FT4) 1
- Free T3 or total T3 should be added when TSH is suppressed but FT4 is normal to rule out T3 toxicosis 1, 2
- Testing should be performed in the morning (around 8 am) when possible for more accurate results 1
Additional Testing Based on Initial Results
If Low TSH with Normal FT4:
- Consider thyroid antibody testing, particularly thyroid stimulating hormone receptor antibody (TRAb) or thyroid stimulating immunoglobulin (TSI) to evaluate for Graves' disease 1
- Thyroid peroxidase (TPO) antibody testing to help identify autoimmune thyroiditis 1
- Repeat thyroid function tests in 2-3 weeks to monitor for progression to overt hyperthyroidism 1
If Low TSH with Low FT4:
- This pattern suggests central hypothyroidism (pituitary dysfunction)
- Morning ACTH and cortisol levels should be measured to evaluate for hypophysitis or pituitary dysfunction 1
- Consider additional pituitary hormone testing including FSH, LH, and sex hormones (testosterone in men, estradiol in women) 1
- MRI of the sella with pituitary cuts should be considered, especially if other pituitary hormones are abnormal 1
If Low TSH with High FT4:
- Radioactive iodine uptake scan (RAIUS) or Technetium-99m thyroid scan (if recent iodinated contrast was used) to differentiate between destructive thyroiditis and Graves' disease 1
- Complete blood count and liver function tests to assess for systemic effects of hyperthyroidism 1
Special Considerations
- In patients on immune checkpoint inhibitors (ICPIs), low TSH may indicate immune-related thyroiditis or hypophysitis, requiring more frequent monitoring 1
- In elderly patients, a low TSH with normal FT4 may be a normal finding and less predictive of clinical hyperthyroidism 3
- In patients with non-thyroidal illness (severe acute or chronic illness), TSH remains the most reliable test to differentiate from true thyroid dysfunction 4
Timing of Follow-up Testing
- For patients with atrial fibrillation, cardiac disease, or other serious medical conditions, repeat testing within 2 weeks 1
- For patients with TSH between 0.1-0.45 mIU/L without cardiac conditions, repeat testing in 3 months 1
- For patients with TSH <0.1 mIU/L, repeat testing within 4 weeks 1
- For patients on immune checkpoint inhibitors, consider monitoring thyroid function every 2-3 weeks initially 1
Common Pitfalls to Avoid
- Do not rely on T3 testing alone for patients on levothyroxine therapy with suppressed TSH, as T3 levels are often normal even in over-replacement 5
- Avoid ordering unnecessary thyroid antibody tests when the diagnosis is clear from TSH and FT4 results 6
- Remember that a single low TSH has poor positive predictive value for hyperthyroidism (only 12%), especially in older adults, and should be confirmed with FT4 measurement 3
- In patients with both adrenal insufficiency and hypothyroidism, steroids should always be started prior to thyroid hormone to avoid precipitating an adrenal crisis 1