Blood Spot Thyroids

Thyroid-stimulating hormone is a glycoprotein secreted by anterior pituitary thyrotrophs in response to thyrotropin-releasing hormone. It binds to receptors on thyroid follicular cells and drives synthesis and release of thyroxine and triiodothyronine. TSH secretion is governed by negative feedback from circulating free thyroid hormones, so even small changes in thyroid function produce reciprocal changes in TSH that are several-fold larger in magnitude.

TSH is the most sensitive single screening marker for primary thyroid dysfunction. Elevation signals primary hypothyroidism, while suppression points to hyperthyroidism or overreplacement. Because pituitary TSH secretion is logarithmically responsive to free hormone levels, TSH amplifies small thyroid changes and is the preferred first-line test in community screening. In secondary (central) hypothyroidism TSH is inappropriately normal or low despite low thyroid hormones.

Thyroxine is the principal secretory product of the thyroid gland, circulating almost entirely bound to carrier proteins (thyroid-binding globulin, albumin, and transthyretin). The small unbound fraction — free T4 — is biologically active and available for cellular uptake and peripheral conversion to triiodothyronine. Free T4 measurement circumvents the influence of binding-protein variation on total hormone concentration.

Free T4 confirms and quantifies the degree of thyroid dysfunction suggested by TSH. Low free T4 with high TSH defines overt primary hypothyroidism; normal free T4 with high TSH is subclinical hypothyroidism. Elevated free T4 with suppressed TSH indicates hyperthyroidism. Free T4 is essential for diagnosing secondary hypothyroidism, where both TSH and free T4 are low or inappropriately normal.

Triiodothyronine is the most metabolically active thyroid hormone, generated predominantly by peripheral 5'-deiodination of thyroxine in liver, kidney, and other tissues. Like T4, T3 circulates largely protein-bound, and the free fraction reflects tissue-available hormone. Because local deiodinase activity determines intracellular T3, serum free T3 is an imperfect proxy for tissue thyroid status.

Free T3 adds diagnostic value in suspected T3 thyrotoxicosis, where TSH is suppressed but free T4 remains normal, and in monitoring combination T4/T3 replacement therapy. Low free T3 may be seen in hypothyroidism, but also in non-thyroidal illness and states of reduced deiodinase activity (selenium deficiency, chronic stress, caloric restriction), so interpretation requires clinical context.

Thyroid peroxidase is a membrane-bound enzyme essential for iodination of thyroglobulin and coupling of iodotyrosines to form thyroid hormones. Antibodies to TPO are a hallmark of autoimmune thyroid disease, reflecting T-cell-mediated autoimmunity and predicting progressive follicular destruction.

Anti-TPO is the most sensitive marker of autoimmune thyroid disease. It is positive in the majority of patients with Hashimoto thyroiditis and many with Graves disease. Presence of anti-TPO antibodies predicts progression from subclinical to overt hypothyroidism and identifies women at higher risk of postpartum thyroiditis. Titre does not reliably correlate with disease severity or guide treatment, so serial quantitation is not routinely indicated.

Thyroglobulin is a large glycoprotein synthesised by thyroid follicular cells, serving as the scaffold for thyroid hormone synthesis. Antibodies to thyroglobulin are found in autoimmune thyroid disease and can interfere with serum thyroglobulin measurement used in thyroid cancer surveillance.

Anti-Tg is less sensitive than anti-TPO but often coexists in Hashimoto thyroiditis. Its principal clinical role is in the follow-up of differentiated thyroid cancer, where it can interfere with immunometric thyroglobulin assays and produce falsely low or undetectable results. When positive, liquid chromatography–tandem mass spectrometry thyroglobulin measurement may be required for accurate tumour-marker surveillance.