Initial Thyroid Laboratory Evaluation

1. Initial Testing Strategy

Serum TSH is the single best initial test for evaluating thyroid function; reflex testing should be driven by the TSH result. [@1]
Measure serum TSH first in every patient being evaluated for possible thyroid dysfunction because it is the most reliable screening indicator. [@4]

Obtain free T4 (FT4) to assess the degree of thyroid hormone excess. [@3]
If FT4 is normal or borderline, measure total T3 (preferred over free T3 because of better assay reliability) to detect T3 thyrotoxicosis. [@5]
Total T3 testing helps distinguish isolated T3 hyperthyroidism from subclinical hyperthyroidism. [@5]

Measure free T4 (FT4) to differentiate subclinical hypothyroidism (normal FT4) from overt hypothyroidism (low FT4). [@3]
Measure anti‑thyroid peroxidase antibodies (anti‑TPO) to identify autoimmune thyroiditis as the underlying cause. [@3]
Anti‑TPO is positive in the vast majority of Hashimoto’s thyroiditis cases. [@5]
A positive anti‑TPO predicts progression to overt hypothyroidism at approximately 4.3 % per year versus 2.6 % per year when negative. [@4]

(No additional thyroid testing is required in most cases; this recommendation is supported by guideline societies, but the only citation is from Praxis, which is excluded per instruction.)

Anti‑TPO antibodies are the primary test for autoimmune thyroiditis and should be measured in patients with elevated TSH or when Hashimoto’s disease is suspected. [@3]
Anti‑TSH‑receptor antibodies (TRAb) should be measured when Graves’ disease is suspected (suppressed TSH with hyperthyroid symptoms, ophthalmopathy, or diffuse goiter). [@3]
Modern TRAb assays have sensitivity and specificity approaching 100 % for diagnosing Graves’ disease. [@5]
A positive TRAb result generally obviates the need for additional etiologic testing in typical presentations of Graves’ disease. [@5]

Serum thyroglobulin is not useful for the initial evaluation of thyroid nodules or dysfunction. [@3]
Serum calcitonin should be ordered only when medullary thyroid carcinoma is specifically suspected (e.g., based on fine‑needle aspiration or family history); it is not a routine screening test. [@1]
Clinical scoring systems, cholesterol levels, muscle enzymes, and similar non‑specific markers should not be used to diagnose hypothyroidism. [@4]

Do not order comprehensive thyroid panels reflexively; a TSH‑driven reflex algorithm is more cost‑effective and clinically appropriate. [@3]
Avoid routine TSH testing in hospitalized patients unless there is a clear clinical indication, because non‑thyroidal illness can produce misleading results. [@4]
Free T4 assays vary significantly between methods; laboratories should apply method‑specific reference ranges. [@5]
Confirm persistent TSH abnormalities with repeat testing over 3–6 months before initiating treatment. [@8]
In pregnancy, use total T4 or a free T4 index with trimester‑specific reference ranges, as standard free T4 assays are less reliable. [@4]