What labs do you check with an elevated Thyroid-Stimulating Hormone (TSH) level?

Laboratory Workup for Elevated TSH

When TSH is elevated, immediately check free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4), as this distinction fundamentally determines treatment urgency and approach. 1

Initial Confirmation Testing

Before pursuing additional workup, confirm the elevated TSH is persistent rather than transient:

• Repeat TSH measurement after 3-6 weeks along with free T4, as 30-60% of initially elevated TSH values normalize spontaneously on repeat testing 1
• Single abnormal values should never trigger treatment decisions without confirmation 1
• For patients with cardiac disease, atrial fibrillation, or serious medical conditions, consider repeating within 2 weeks rather than waiting the full 3-6 weeks 1

Essential Laboratory Tests

Once elevated TSH is confirmed, obtain the following:

Free T4 (Free Thyroxine)

• Distinguishes subclinical from overt hypothyroidism - elevated TSH with normal free T4 indicates subclinical disease, while low free T4 indicates overt hypothyroidism requiring immediate treatment 1, 2
• Free T4 is superior to total T4 because it is not affected by thyroid-binding protein abnormalities that can produce misleading results 2
• Use equilibrium dialysis method when available for most accurate measurement 3

Anti-TPO Antibodies (Thyroid Peroxidase Antibodies)

• Identifies autoimmune etiology (Hashimoto's thyroiditis) and predicts progression risk to overt hypothyroidism 1
• Patients with positive anti-TPO antibodies have 4.3% annual progression rate versus 2.6% in antibody-negative individuals 1
• This higher progression risk influences treatment decisions, particularly for TSH levels between 4.5-10 mIU/L 1

Additional Tests Based on Clinical Context

For Women of Childbearing Age or Planning Pregnancy

• No additional thyroid tests needed beyond TSH and free T4, but treatment threshold is lower 1
• Subclinical hypothyroidism during pregnancy is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring 1

For Suspected Central Hypothyroidism

If TSH is low or inappropriately normal despite symptoms suggesting hypothyroidism:

• Free T4 by equilibrium dialysis - will be low in central hypothyroidism despite low/normal TSH 3
• ACTH and cortisol levels (morning sample or 1 mcg cosyntropin stimulation test) - adrenal insufficiency frequently coexists and must be identified before starting thyroid replacement 3, 4
• MRI of sella with pituitary cuts - evaluates for hypophysitis, pituitary tumor, or other structural abnormalities 3
• FSH, LH, and gonadal hormones - assesses for panhypopituitarism 3

Lipid Profile

• Review existing lipid panel or obtain one, as subclinical hypothyroidism may affect cholesterol levels 1
• Treatment with levothyroxine may lower LDL cholesterol in patients with TSH >10 mIU/L 1

Tests That Are NOT Routinely Indicated

Free T3 or Total T3

• Not useful for diagnosing hypothyroidism - T3 levels remain normal until late in disease progression 1, 5
• T3 measurement is primarily useful for diagnosing hyperthyroidism or monitoring certain patients on thyroid replacement 5

TSH Receptor Antibodies (TRAb) or Thyroid Stimulating Immunoglobulins (TSI)

• Not indicated for elevated TSH - these antibodies cause hyperthyroidism (Graves' disease), not hypothyroidism 6

Thyroglobulin

• Not useful for diagnosing primary hypothyroidism 5
• Reserved for monitoring thyroid cancer patients after thyroidectomy 5

Thyroid Uptake and Scan

• Not indicated for elevated TSH workup 7
• Primarily useful for evaluating hyperthyroidism and nodular thyroid disease 5

Critical Pitfalls to Avoid

• Never treat based on single elevated TSH without confirmation - transient elevations are common during recovery from nonthyroidal illness 1
• Always check free T4, not just TSH - TSH alone cannot distinguish subclinical from overt hypothyroidism or identify central hypothyroidism 1, 3
• Rule out adrenal insufficiency before starting thyroid hormone in patients with suspected central hypothyroidism or pituitary disease - starting levothyroxine before corticosteroids can precipitate life-threatening adrenal crisis 3, 4
• Consider recent iodine exposure (CT contrast) which can transiently affect thyroid function tests 1
• Recognize that acute illness, hospitalization, and certain medications can transiently elevate TSH without true hypothyroidism 1

Algorithm Summary

1. Confirm elevated TSH with repeat measurement in 3-6 weeks (or 2 weeks if urgent clinical concern)
2. Measure free T4 simultaneously with repeat TSH
3. Check anti-TPO antibodies to identify autoimmune etiology and assess progression risk
4. If TSH >10 mIU/L with low free T4: Overt hypothyroidism - initiate levothyroxine immediately 1
5. If TSH >10 mIU/L with normal free T4: Subclinical hypothyroidism - initiate levothyroxine regardless of symptoms 1
6. If TSH 4.5-10 mIU/L with normal free T4: Subclinical hypothyroidism - consider treatment if symptomatic, positive anti-TPO antibodies, or planning pregnancy; otherwise monitor every 6-12 months 1
7. If low/normal TSH with low free T4: Suspect central hypothyroidism - obtain ACTH, cortisol, and pituitary MRI before initiating treatment 3