What is the initial step in a hypothyroid (underactive thyroid) workup?

Hypothyroid Workup

Initial Laboratory Testing

The initial step in a hypothyroid workup is to measure serum TSH, which is the single most sensitive screening test for primary hypothyroidism with sensitivity above 98% and specificity greater than 92%. 1, 2

• TSH is the preferred first-line test for evaluating suspected primary hypothyroidism, as it detects thyroid dysfunction earlier than thyroid hormone levels themselves 2, 3
• If TSH is elevated, measure free T4 to distinguish between subclinical hypothyroidism (normal free T4) and overt hypothyroidism (low free T4) 1, 2
• Confirm any initially elevated TSH with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1, 4

Diagnostic Algorithm Based on Initial Results

If TSH is Elevated with Low Free T4 (Overt Hypothyroidism)

• This confirms primary hypothyroidism requiring levothyroxine replacement therapy 3
• Consider measuring anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk and may influence treatment decisions 1, 4

If TSH is Elevated with Normal Free T4 (Subclinical Hypothyroidism)

• Repeat TSH and free T4 after 2-3 months to confirm persistence 4
• Measure anti-TPO antibodies, as positive antibodies indicate 4.3% annual progression risk versus 2.6% in antibody-negative individuals 1
• Treatment decisions depend on TSH level: initiate levothyroxine for TSH >10 mIU/L regardless of symptoms, but individualize treatment for TSH 4.5-10 mIU/L based on symptoms, antibody status, and patient factors 1, 4, 3

If Free T4 is Low with Normal or Low TSH (Central Hypothyroidism)

• This pattern suggests pituitary or hypothalamic dysfunction rather than primary thyroid disease 5
• Obtain morning pituitary hormone panel (ACTH, cortisol, LH, FSH, testosterone/estrogen) and MRI of the sella with pituitary cuts 5
• Critical: Evaluate and treat adrenal insufficiency FIRST before starting thyroid hormone replacement, as initiating levothyroxine without addressing concurrent adrenal insufficiency can precipitate life-threatening adrenal crisis 6, 5

What NOT to Do

There is no role for imaging in the workup of primary hypothyroidism in adults—ultrasound, CT, MRI, PET/CT, or radioiodine uptake scans do not help differentiate among causes of hypothyroidism and should not be ordered. 6

• Imaging for thyroid morphology does not change management, as all causes of hypothyroidism will have decreased radioiodine uptake 6
• Physical examination alone cannot reliably diagnose or exclude hypothyroidism (likelihood ratios too low to be clinically useful), making laboratory confirmation essential 7
• Do not measure T3 levels in initial evaluation of suspected primary hypothyroidism, as T3 remains normal until late in disease progression 2

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing, as transient elevations are common and frequently normalize 1
• Never start thyroid hormone replacement before ruling out adrenal insufficiency in patients with suspected central hypothyroidism, as this can trigger adrenal crisis 6, 5
• Avoid ordering thyroid imaging studies, as they provide no diagnostic value in hypothyroidism workup 6
• Do not rely on clinical symptoms alone to diagnose hypothyroidism, as symptoms are nonspecific and overlap with many other conditions 3, 7