A complete first-pass thyroid panel is smaller than most people expect. TSH, free T4 and TPO antibodies answer the three questions that matter at the start: is thyroid function abnormal, how abnormal, and is autoimmunity the reason. Everything beyond that is added for a specific clinical question rather than ordered by default.

The core three tests

TSH is the screening test because it changes first and by the largest proportion. Free T4 measures the unbound hormone available to tissues and separates overt from subclinical disease. TPO antibodies identify autoimmune thyroid disease, which is the most common cause of hypothyroidism in iodine-sufficient countries. The National Institute of Diabetes and Digestive and Kidney Diseases describes thyroid peroxidase antibodies as present in most people with Hashimoto's disease.

When T3 is worth adding

T3 testing earns its place in suspected hyperthyroidism. The 2016 American Thyroid Association hyperthyroidism guideline recommends that serum TSH, free T4 and total T3 all be assessed at the initial evaluation of suspected thyrotoxicosis, because T3 can be raised while free T4 is still normal. In hypothyroidism, T3 adds little. The American Thyroid Association describes T3 as the last test to become abnormal in an underactive thyroid, so a normal T3 does not rule hypothyroidism out and a low-normal T3 does not confirm it.

What to leave off the panel

Reverse T3 is the most commonly added test with the least justification. The American Thyroid Association states that "in healthy, non-hospitalized people, measurement of reverse T3 does not help determine whether hypothyroidism exists or not, and is not clinically useful." Thyroglobulin antibodies are reasonable when TPO antibodies are negative but autoimmune disease is still suspected, and they matter greatly after thyroid cancer surgery, but they rarely change management otherwise. Routine thyroid ultrasound in someone with a normal examination and normal TSH finds incidental nodules that then generate more testing.

Test	Order it when	Skip it when
TSH	Always, first line	Never skip
Free T4	TSH abnormal, pituitary disease suspected, or on treatment	Rarely
TPO antibodies	Once, to establish the cause	Repeating them to track disease
Total or free T3	Suspected hyperthyroidism	Routine hypothyroid workup
Reverse T3	Not recommended in outpatients	Essentially always
Thyroid ultrasound	Palpable nodule, goitre, neck mass	Symptoms alone with normal labs

Ask for TSH, free T4 and TPO antibodies on one draw, and ask what each result would change. Bring a list of supplements, since biotin can distort every one of these assays. If the panel is normal and you still feel unwell, the next step is looking outside the thyroid rather than adding more thyroid tests.

Free T4 by immunoassay is affected by binding protein changes in pregnancy, oestrogen therapy and severe illness. Equilibrium dialysis or liquid chromatography tandem mass spectrometry is more accurate in those settings but is not needed routinely. Total T3 outperforms free T3 assays for diagnosing thyrotoxicosis and is what the 2016 American Thyroid Association guideline specifies for initial evaluation.

TPO antibody positivity is common and not itself a disease: 11.3 percent of the NHANES III disease-free reference population tested positive. The American Thyroid Association states that "repeating and monitoring your thyroid antibody levels is not needed," because TSH and free T4 report actual thyroid function. Thyrotropin receptor antibody, not TPO, is the antibody that establishes Graves' disease. High-dose biotin can invalidate TSH, free T4, T3 and thyroglobulin assays; the American Thyroid Association advises stopping it for at least two days before thyroid testing.

What tests belong in a complete thyroid panel?

The core three tests

When T3 is worth adding

What to leave off the panel

Sources

The core three tests

When T3 is worth adding

What to leave off the panel

Sources

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