Exam-focused guide to etiologic testing in thyrotoxicosis for Family Medicine: when to order TSH, free T4, and TRAb for boards.
Start with TSH and free T4; if TSH is suppressed, measure thyrotropin receptor antibodies (TRAb) to distinguish Graves disease from other causes — this testing sequence is commonly tested on Family Medicine board exams.
A 35-year-old man presents to you with agitation and tremor. He has no past medical history and takes no medications. He smokes a half-pack of cigarettes per day and drinks alcohol socially, but he does not use illicit drugs. He works as a baker. His review of systems is positive for diarrhea, heat intolerance, and decreased libido.
His vital signs are: temperature 37.9 °C, heart rate 110 beats/minute, blood pressure 110/75 mm Hg, respiratory rate 14 breaths/minute, and oxygen saturation 99% on room air. Findings on a head, eyes, ears, nose, and throat examination are normal. His thyroid is diffusely enlarged, without tenderness or discrete nodules. His heart is rapid but regular without murmurs. His lungs are clear, and his abdomen is benign. He has a fine intention tremor.
His laboratory values show a thyroid-stimulating hormone (TSH) level of < 0.01 mIU/mL (normal range, 0.5-5 mIU/mL) and a free thyroxine (T4) level of 30 ng/dL (normal range, 0.9-2.3 ng/dL).
Of the following, which tests are appropriate as the next step in the workup of this patient?
Answer Options:
A. radioactive iodine uptake (RAIU)
ATA 2016 recommends any one of TRAb, RAIU, or thyroid Doppler ultrasound to determine the cause of thyrotoxicosis. In a patient with overt thyrotoxicosis, diffuse goiter, and no orbitopathy or nodules, measuring TRAb is an appropriate—and often most cost-effective—first test. ETA 2018 similarly endorses TRAb as a first-line test to confirm Graves disease; RAIU is reasonable if TRAb is unavailable, indeterminate, or nodularity is suspected.
This question tests whether you can distinguish the “etiology workup” step in hyperthyroidism from general autoimmune thyroid testing. In overt thyrotoxicosis with diffuse goiter and no nodules, ATA (2016) and ETA (2018) recommend TRAb, RAIU, or Doppler ultrasound to determine cause; TRAb is highly specific for Graves, rapid, and avoids radiation exposure and scheduling delays, making it a common first choice.
Candidates often select RAIU reflexively because it classically separates Graves (high uptake) from thyroiditis (low uptake). While RAIU is acceptable, TRAb is equally guideline-concordant and frequently preferred initially when Graves is suspected and the exam lacks nodules.
| Option | What It Tests / Implies | Why It’s Wrong Here |
|---|---|---|
| RAIU | Recognizing scintigraphy stratifies etiologies by uptake pattern | Reasonable alternative per ATA/ETA, but TRAb is a guideline-supported, rapid, radiation-free first test when Graves is suspected without nodules. |
| Comprehensive urinalysis | Non-specific screening | No role in diagnosing cause of thyrotoxicosis. |
| Thyroid peroxidase antibodies | Autoimmune thyroiditis (Hashimoto) marker | Not specific for Graves; does not reliably determine cause of thyrotoxicosis. |
| TRAb | Graves-specific etiologic test | Correct: High specificity; guideline-endorsed first-line in this scenario. |
In overt thyrotoxicosis with diffuse goiter and no nodules, TRAb measurement is a guideline-endorsed, radiation-free first test to confirm Graves disease.
Boards expect you to distinguish Graves-specific testing (TRAb) from generic autoimmune markers (TPO) and to recognize when TRAb can replace RAIU as the initial etiologic test—especially when the presentation strongly suggests Graves and there are no nodules.
A 28-year-old woman with palpitations, tremor, and diffuse non-tender goiter; TSH undetectable, free T4 elevated; no eye findings; not pregnant. Best initial test to determine etiology?
A. Thyroid ultrasound with DopplerA 42-year-old man with neck pain, elevated ESR, tender thyroid, TSH <0.01, elevated free T4. Which test best differentiates subacute thyroiditis from Graves?
A. Radioactive iodine uptake (RAIU)A 10-week pregnant patient with overt thyrotoxicosis and diffuse goiter. Best test to confirm Graves etiology?
A. RAIUA 63-year-old with thyrotoxicosis and palpable nodules. Next best test to determine etiology?
A. RAIU scanA 70-year-old on amiodarone develops thyrotoxicosis. Best initial approach to determine type 1 vs type 2 AIT?
A. Color-flow Doppler ultrasound of the thyroid
Compare your diagnostic approach to overt thyrotoxicosis in three scenarios: (1) diffuse goiter without nodules; (2) painful tender thyroid with elevated ESR; (3) pregnancy. Which tests (TRAb, RAIU, Doppler) are preferred, and why?
Boards expect recognition that TRAb is first-line when Graves is suspected without nodules, including during pregnancy (ATA 2016; ETA 2018).
When nodularity is present or Graves vs thyroiditis is unclear and pregnancy is not a factor; RAIU provides functional differentiation.
No. TPO indicates autoimmune thyroid disease broadly and lacks specificity for Graves; boards expect TRAb for Graves confirmation.
No. Reserve for suspected nodules or to assess vascularity in selected scenarios (e.g., amiodarone-induced thyrotoxicosis).
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