What is the appropriate diagnostic work‑up for Hashimoto’s thyroiditis in an adult woman (30‑60 years)?

Diagnostic Work-Up for Hashimoto's Thyroiditis

The diagnosis of Hashimoto's thyroiditis in adult women (30-60 years) requires measurement of TSH, free T4, and anti-thyroid antibodies (anti-TPO and anti-thyroglobulin), combined with thyroid ultrasound when antibodies are positive or TSH is elevated. 1

Initial Laboratory Testing

Measure TSH as the first-line screening test, which has a sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 2. If TSH is elevated, immediately measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 2.

Antibody Testing

• Check anti-thyroid peroxidase (anti-TPO) antibodies and anti-thyroglobulin (TgAb) antibodies in all patients with elevated TSH or clinical suspicion of Hashimoto's thyroiditis 1, 3
• Anti-TPO antibodies are the primary diagnostic marker, present in the vast majority of Hashimoto's cases 1, 3
• Anti-thyroglobulin antibodies should also be measured, as TgAb levels correlate with symptom burden (r = 0.25, p = 0.0001) even in patients without levothyroxine therapy 4
• Positive antibodies confirm autoimmune etiology and predict a 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative individuals 2

Confirmatory Testing

Repeat TSH and free T4 after 3-6 weeks if initially elevated, as 30-60% of elevated TSH values normalize spontaneously 2. This step prevents unnecessary treatment of transient thyroiditis or recovery-phase thyroid dysfunction 2.

Imaging Studies

Perform thyroid ultrasound when antibodies are positive or TSH is persistently elevated 3. The characteristic ultrasound findings in Hashimoto's thyroiditis include:

• Hypoechogenic (darkened) thyroid parenchyma 3
• Inhomogeneous (patchy, irregular) echotexture throughout the gland 3
• These findings reflect the lymphocytic infiltration that defines the disease histologically 1

Fine Needle Aspiration Biopsy

Fine needle aspiration biopsy is NOT routinely required for diagnosis when clinical presentation, positive antibodies, and characteristic ultrasound findings are present 1, 3. Reserve cytological examination for:

• Patients with thyroid nodules requiring evaluation for malignancy 5
• Atypical presentations where the diagnosis remains uncertain despite antibody and imaging results 1

When performed, cytology shows lymphoplasmacytic infiltration, lymphoid follicles with germinal centers, and the presence of Askanazy (Hürthle) cells 1.

Clinical Assessment

Document specific hypothyroid symptoms that correlate with elevated antibody levels 4, 6:

• Chronic fatigue (most common and significantly associated with elevated TgAb, p = 0.0001) 4, 6
• Fragile or dry hair (significantly associated with TgAb levels, p = 0.0043) 4, 6
• Facial edema (p = 0.0061) and periorbital edema (p = 0.0293) 4
• Harsh or hoarse voice (p = 0.0349) 4
• Chronic irritability and nervousness 6
• Cold intolerance, weight gain, constipation 2

Importantly, symptom burden in Hashimoto's thyroiditis correlates with antibody levels independent of TSH or thyroid hormone levels 4, 6. Women with anti-TPO levels >121.0 IU/mL report significantly more symptoms (6.7 ± 2.5 vs. 4.1 ± 2.8, p < 0.001) than those with lower antibody levels, even when both groups are euthyroid 6.

Screening for Associated Autoimmune Conditions

Screen for other autoimmune diseases, as Hashimoto's thyroiditis frequently occurs with 3:

• Type 1 diabetes mellitus 3
• Addison's disease (adrenal insufficiency) 3
• Vitiligo 3
• These often present as polyglandular autoimmune syndrome type 2 3

Before initiating levothyroxine in patients with suspected central hypothyroidism or multiple autoimmune conditions, always check morning cortisol and ACTH to exclude adrenal insufficiency, as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 2.

Common Diagnostic Pitfalls

• Do not treat based on a single elevated TSH value—confirm with repeat testing, as transient elevations are common 2
• Do not assume normal TSH excludes Hashimoto's thyroiditis—patients can be antibody-positive and euthyroid for years before developing hypothyroidism 1, 7
• Do not overlook TgAb measurement—checking only anti-TPO misses patients whose symptom burden correlates specifically with thyroglobulin antibodies 4
• Recognize that symptom burden may be driven by autoimmunity itself, not just hypothyroidism—patients with high antibody titers report more symptoms even when TSH and free T4 are normal 4, 6

Treatment Threshold After Diagnosis

Initiate levothyroxine therapy for TSH >10 mIU/L regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism 2. For TSH 4.5-10 mIU/L with positive anti-TPO antibodies, consider treatment especially in symptomatic patients, those planning pregnancy, or those with goiter 2.

Even in euthyroid patients with confirmed Hashimoto's thyroiditis (positive antibodies, normal TSH), prophylactic levothyroxine therapy reduces thyroid volume, decreases antibody titers, and may prevent progression 7. After 15 months of treatment, anti-TPO and anti-thyroglobulin antibody levels decrease significantly, and thyroid volume decreases rather than increases 7.