What is the initial lab workup for a patient with elevated Thyroid-Stimulating Hormone (TSH) levels?

Initial Laboratory Workup for Elevated TSH

For patients with elevated TSH, the initial laboratory workup should include measurement of free thyroxine (FT4) to distinguish between subclinical and overt hypothyroidism. 1

Primary Assessment

• TSH and FT4 should be used together for case detection in symptomatic patients with suspected hypothyroidism 1
• If the initial TSH is elevated but FT4 has not been measured, repeat TSH along with FT4 measurement at a minimum of 2 weeks but no longer than 3 months after the initial assessment 1
• Low TSH with a low FT4 is consistent with central hypothyroidism, which requires evaluation for pituitary dysfunction 1
• Normal FT4 with elevated TSH indicates subclinical hypothyroidism 1
• Low FT4 with elevated TSH confirms overt (primary) hypothyroidism 1, 2

Follow-up Testing

• Evaluate for signs and symptoms of hypothyroidism, previous treatment for hyperthyroidism, thyroid gland enlargement, or family history of thyroid disease 1
• Consider measuring thyroid peroxidase antibodies (anti-TPO) to identify autoimmune etiology, which predicts a higher risk of developing overt hypothyroidism (4.3% per year vs. 2.6% per year in antibody-negative individuals) 1
• Review lipid profiles, as hypothyroidism can affect cholesterol levels 1
• Special consideration should be given to women who are pregnant or planning pregnancy 1

Interpretation Based on TSH Levels

For TSH between 4.5 and 10 mIU/L (mild elevation):

• If asymptomatic, monitor TSH every 4-6 weeks as part of routine care 1
• Consider treatment in symptomatic patients, patients with infertility, and patients with goiter or positive anti-TPO antibodies 2, 3

For TSH persistently >10 mIU/L:

• Treatment is recommended regardless of symptoms, especially in younger patients (<65-70 years) 1, 2, 3
• Monitor TSH every 6-8 weeks while titrating hormone replacement to goal TSH within the reference range 1
• FT4 can help interpret ongoing abnormal TSH levels on therapy, as TSH may take longer to normalize 1

Special Considerations

• Age-specific reference ranges for TSH should be considered for older adults 3
• In patients >80-85 years with TSH ≤10 mIU/L, a wait-and-see strategy may be appropriate 3
• For patients on immune checkpoint inhibitor therapy, TSH and FT4 should be checked every 4-6 weeks as part of routine monitoring 1
• T3 testing is generally not needed in the initial workup of hypothyroidism but may be helpful in specific situations such as when hyperthyroidism is suspected with suppressed TSH 4, 5

Common Pitfalls to Avoid

• Relying solely on TSH without measuring FT4 can lead to misdiagnosis, as low TSH could indicate either hyperthyroidism or central hypothyroidism 1
• Not repeating abnormal tests for confirmation before initiating treatment 1
• Overtreatment of subclinical hypothyroidism in elderly patients, which may increase risk of atrial fibrillation and osteoporosis 2
• Failing to consider non-thyroidal illness or medication effects that can alter TSH levels 1
• Not recognizing that elevated TSH can be seen in the recovery phase of thyroiditis 1

By following this systematic approach to laboratory evaluation of elevated TSH, clinicians can accurately diagnose thyroid dysfunction and initiate appropriate management to prevent long-term complications associated with untreated hypothyroidism.