What laboratory studies should be ordered if Thyroid-Stimulating Hormone (TSH) is low?

Laboratory Studies to Order When TSH is Low

When TSH is low, free T4 (FT4) should be ordered as the primary follow-up test to determine the cause and severity of the thyroid dysfunction. 1

Diagnostic Algorithm for Low TSH

1. Initial finding: Low TSH

   • First step: Order free T4 (FT4) test

2. Interpretation of results:

   • Low TSH + High FT4 = Hyperthyroidism 1
   • Low TSH + Normal FT4 = Subclinical hyperthyroidism or early hyperthyroidism
   • Low TSH + Low FT4 = Central hypothyroidism (pituitary or hypothalamic dysfunction) 1

3. Additional testing based on FT4 results:

   • If FT4 is normal but clinical suspicion for hyperthyroidism remains high:
     • Order free T3 (FT3) to evaluate for T3 thyrotoxicosis 2
     • T3 thyrotoxicosis is most likely when TSH is severely suppressed (<0.01 μIU/mL) 2

Clinical Considerations

• Free T3 testing has limited utility in most patients and should be reserved for cases where TSH is significantly suppressed (<0.01 μIU/mL) with normal or low FT4 2

• Consider thyroid antibody testing:

  • Thyroid-stimulating immunoglobulin (TSI) for suspected Graves' disease
  • Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) antibodies if autoimmune thyroid disease is suspected 1

• TSH levels correlate inversely with TSI levels in Graves' disease, with lower TSH indicating higher TSI activity 3

Special Situations

• Acute illness: Thyroid function tests may be misleading during acute illness (euthyroid sick syndrome). Consider repeating tests after metabolic stability is achieved 1

• Older adults: Low TSH is common in older adults without hyperthyroidism. In patients >60 years with low TSH:

  • If FT4 is clearly normal (<129 nmol/L), hyperthyroidism is unlikely 4
  • Consider repeating TSH measurement before initiating treatment 4

• Monitoring frequency:

  • For TSH between 0.1-0.45 mIU/L: monitor every 3 months
  • For TSH <0.1 mIU/L: monitor every 4-6 weeks 1

Common Pitfalls

• Failing to order FT4 along with TSH can lead to misdiagnosis or delayed diagnosis
• Over-reliance on TSH alone without considering clinical context
• Not recognizing central hypothyroidism (low TSH with low FT4) as a possible diagnosis
• Unnecessary FT3 testing when TSH is only mildly suppressed and FT4 is normal 2
• Not accounting for the effect of acute illness on thyroid function tests 5

Remember that interpretation of thyroid function tests should always be done in the clinical context, considering the patient's symptoms, medical history, and medication use.