Clinical commentary
## Diagnostic approach
The biochemical diagnosis of Hashimoto's thyroiditis rests on three pillars: thyroid function tests demonstrating hypothyroidism (or progression toward it), positive thyroid autoantibodies confirming autoimmune aetiology, and clinical correlation excluding other causes of thyroid dysfunction. Practitioners should be aware that approximately 5–15% of patients with biochemically confirmed Hashimoto's have negative TPO and thyroglobulin antibodies at presentation — antibody-negative Hashimoto's remains a recognized clinical entity diagnosed on imaging characteristics and biopsy.
Typical biochemical evolution follows a predictable pattern. Early disease often shows normal or modestly elevated TSH with positive antibodies; this progresses through subclinical hypothyroidism (elevated TSH, normal Free T4) to overt hypothyroidism (elevated TSH, low Free T4). The rate of progression averages 2–4% per year for antibody-positive subclinical hypothyroidism, but accelerates in pregnancy, with significant stressors, and in patients with high antibody titres.
## Companion biomarker interpretation
TPO antibody titre correlates loosely with disease activity but should not be used to track treatment response — antibody levels can persist for years even with effective hormone replacement. Thyroglobulin antibodies are clinically meaningful in two specific contexts: confirming the autoimmune diagnosis when TPO antibodies are negative, and interfering with thyroglobulin measurement in thyroid cancer surveillance. Practitioners should not order serial antibody measurements once the diagnosis is confirmed unless evaluating progression toward a different autoimmune phenotype.
## Special considerations
Pregnancy assessment is the highest-priority clinical context. Trimester-specific TSH reference ranges should be applied (less than 2.5 mIU/L first trimester; less than 3.0 mIU/L second and third trimesters). Antibody-positive women with TSH greater than 2.5 mIU/L in the first trimester benefit from levothyroxine treatment to reduce miscarriage risk per ATA 2017 guidelines. Monitoring during pregnancy should occur every 4 weeks through the first half of gestation and at least once in the third trimester.