What labs should be ordered for a 20-50 year old adult woman with suspected hyperthyroidism and no significant medical history?

Laboratory Testing for Suspected Hyperthyroidism in Young Adult Women

Order TSH as the initial screening test, and if suppressed, follow with free T4 and free T3 to confirm hyperthyroidism and assess severity. 1, 2

Initial Laboratory Panel

First-Line Test

• TSH is the single most sensitive screening test for thyroid dysfunction, with sensitivity of 98% and specificity of 92% 3, 4
• A suppressed TSH (typically <0.1 mIU/L) indicates hyperthyroidism and warrants further testing 1, 2
• TSH alone is insufficient to diagnose hyperthyroidism—you must measure free thyroid hormones to confirm the diagnosis 1, 2

Confirmatory Tests When TSH is Low

• Measure both free T4 (FT4) and free T3 (FT3) to confirm biochemical hyperthyroidism 1, 2
• Free T3 is particularly important because some patients have isolated T3 toxicosis with normal FT4 5, 6
• Overt hyperthyroidism is defined as suppressed TSH with elevated FT4 and/or FT3 2
• Subclinical hyperthyroidism shows suppressed TSH with normal FT4 and FT3 2

Additional Diagnostic Tests to Determine Etiology

TSH Receptor Antibodies (TRAb)

• Order TSH-receptor antibodies to diagnose Graves' disease, which accounts for 70% of hyperthyroidism cases 1
• Positive TRAb confirms Graves' disease and eliminates the need for thyroid scintigraphy in most cases 1, 2

Thyroid Peroxidase Antibodies (TPO)

• Measure TPO antibodies to identify autoimmune thyroid disease 1
• Positive TPO antibodies support Graves' disease or Hashimoto's thyroiditis (which can have a thyrotoxic phase) 1

Thyroid Ultrasound

• Perform thyroid ultrasonography to evaluate for nodules or goiter 1, 2
• Ultrasound helps distinguish between diffuse disease (Graves') and nodular disease (toxic adenoma or toxic multinodular goiter) 1, 2

When to Order Additional Imaging

Thyroid Scintigraphy

• Reserve radioiodine uptake and scan for cases where the diagnosis remains unclear after initial testing or when thyroid nodules are present 1, 2
• Scintigraphy distinguishes between high-uptake conditions (Graves', toxic nodules) and low-uptake conditions (thyroiditis, exogenous thyroid hormone) 1, 2
• This test is not needed if TRAb is positive and clinical presentation is consistent with Graves' disease 1, 2

Critical Pitfalls to Avoid

Common Testing Errors

• Never order only TSH without follow-up free hormone testing when TSH is abnormal—this leaves the diagnosis incomplete 1, 2
• Do not order total T4 or total T3 instead of free hormones, as total hormones are affected by binding protein abnormalities and provide misleading results 5
• Avoid ordering FT3 alone as the initial test—TSH should always be measured first 6, 7
• Do not order thyroid panels reflexively without clinical indication, as this leads to unnecessary costs without improving patient outcomes 7

Interpretation Caveats

• Free T4 may be falsely elevated in patients on amiodarone or levothyroxine therapy, even when euthyroid 5
• In elderly patients, a low TSH is often not associated with true hyperthyroidism and requires careful clinical correlation 6
• Pregnancy, nonthyroidal illness, and certain medications can affect thyroid function test results 5

Algorithmic Approach

1. Measure TSH first in all patients with suspected hyperthyroidism 3, 2
2. If TSH is suppressed (<0.1 mIU/L): Order FT4 and FT3 simultaneously 1, 2
3. If FT4 and/or FT3 are elevated: Order TRAb to confirm Graves' disease 1, 2
4. If TRAb is negative or nodules are present on exam: Order thyroid ultrasound 1, 2
5. If diagnosis remains unclear: Consider thyroid scintigraphy to differentiate etiology 1, 2

This streamlined approach minimizes unnecessary testing while ensuring accurate diagnosis of hyperthyroidism and its underlying cause 7.