Thyroid Function Tests: TSH, Free T4, Free T3—and When You Actually Need Each One

 

Thyroid Function Tests: TSH, Free T4, Free T3—and When You Actually Need Each One

TSH is almost always enough. Free T3 is almost never needed. And sick euthyroid syndrome fools everyone.

This post complements the thyroid antibody workup from earlier in the series. That post covered which antibody to order when you suspect autoimmune thyroid disease. This one covers the function tests—TSH, free T4, and free T3—and the interpretation patterns that trip up clinicians daily.

The Hierarchy: TSH First, Always

TSH is the single best screening test for thyroid dysfunction in outpatient primary care. The pituitary amplifies small changes in thyroid hormone levels, making TSH far more sensitive than direct hormone measurement. A normal TSH essentially rules out primary thyroid disease in an outpatient setting.

TSH	Free T4	Free T3	Interpretation
↑ High	↓ Low	—	Overt hypothyroidism. Treat with levothyroxine.
↑ High	Normal	—	Subclinical hypothyroidism. Repeat in 6–12 weeks to confirm. Treat if TSH >10, or if symptomatic + anti-TPO positive, or if pregnant/trying to conceive.
↓ Low	↑ High	—	Overt hyperthyroidism. Order TSI to confirm Graves'. Consider radioactive iodine uptake if diagnosis unclear.
↓ Low	Normal	↑ High	T3 thyrotoxicosis. One of the few times free T3 is needed. Seen in early Graves' or toxic nodule.
↓ Low	Normal	Normal	Subclinical hyperthyroidism. Repeat to confirm. Consider treatment if TSH <0.1, age >65, atrial fibrillation, or osteoporosis risk.
Normal or Low	↓ Low	—	Central hypothyroidism (pituitary or hypothalamic). TSH is inappropriately normal/low despite low T4. Rare but missed if you only check TSH.
Variable	Variable	—	Sick euthyroid syndrome (nonthyroidal illness). See below.

When to Order Free T3 (Almost Never)

Free T3 is overordered in primary care. The only validated indications:

• Suppressed TSH + normal free T4: Check free T3 to detect T3 thyrotoxicosis
• Monitoring amiodarone-induced thyroid disease (complex T3/T4 dynamics)
• Suspected T3 thyrotoxicosis (early Graves', toxic adenoma)

Free T3 should NOT be ordered for: hypothyroidism monitoring (it's the last to fall and the most variable), fatigue workup, or routine screening. Treat hypothyroidism by normalizing TSH, not by chasing T3 levels.

Sick Euthyroid Syndrome (Nonthyroidal Illness)

Acutely ill hospitalized patients frequently have abnormal thyroid function tests despite having no thyroid disease. The classic pattern: low T3, low or normal T4, low/normal/slightly elevated TSH. This is an adaptive response to illness, not hypothyroidism.

The Rule

Do not check thyroid function tests in acutely ill hospitalized patients unless you have a specific clinical reason to suspect thyroid disease (myxedema coma, thyroid storm, new atrial fibrillation). Abnormal results in acute illness are almost always sick euthyroid and do not warrant treatment. Recheck 6–8 weeks after recovery if needed.

Pregnancy: Trimester-Specific TSH Ranges

TSH normally drops in the first trimester due to HCG-mediated thyroid stimulation. Using non-pregnant reference ranges will over-diagnose hypothyroidism in early pregnancy:

• First trimester: Upper limit of TSH ~4.0 mIU/L (or ideally population-based trimester-specific ranges from your lab, typically 0.1–2.5)
• Second/third trimester: TSH gradually returns toward non-pregnant range
• Gestational thyrotoxicosis: Suppressed TSH with elevated free T4 in the first trimester, driven by high HCG (hyperemesis gravidarum). TSI-negative. Self-limited. Do NOT treat with antithyroid drugs—it's not Graves'.
• Overt hypothyroidism in pregnancy should be treated aggressively (target TSH <2.5 in first trimester). Levothyroxine dose typically increases 25–50% in pregnancy.

The Pitfalls

• Checking only TSH and missing central hypothyroidism: If a patient has symptoms of hypothyroidism + a pituitary history (surgery, radiation, tumor, postpartum hemorrhage/Sheehan's), check free T4 even if TSH is "normal."
• Biotin interference (from the antibody post): Biotin causes falsely low TSH and falsely high free T4, mimicking hyperthyroidism. Stop biotin supplements 48–72 hours before testing.
• Checking TFTs too soon after dose changes: TSH takes 6–8 weeks to re-equilibrate after a levothyroxine dose change. Don't recheck sooner.
• Ordering total T4 instead of free T4: Total T4 is affected by binding protein changes (pregnancy, estrogen, liver disease). Free T4 is the clinically relevant measurement.
• Over-checking in stable patients: Once hypothyroid patients are stable on levothyroxine, annual TSH is sufficient. More frequent testing creates dose-chasing.
• Treating subclinical hypothyroidism reflexively: TSH 5–10 with normal T4 doesn't always need treatment. Consider symptoms, anti-TPO status, age, cardiovascular risk, and fertility plans.

Pediatric Note

Congenital hypothyroidism is screened on the newborn metabolic panel. A high TSH on newborn screen requires urgent confirmatory testing and treatment—delayed treatment causes irreversible intellectual disability. In children, acquired hypothyroidism (usually Hashimoto's) should be suspected with growth deceleration, delayed puberty, fatigue, and constipation. TSH is the first-line test at any age.

Bottom Line

TSH first. Free T4 if TSH is abnormal. Free T3 only for suppressed TSH with normal T4. Don't test acutely ill patients unless you suspect a thyroid emergency. Use trimester-specific ranges in pregnancy. And stop biotin before testing.

Stay sharp out there.