Key takeaway: In overt thyrotoxicosis, order TRAb or RAIU to determine etiology; TRAb is often preferred initially when Graves disease is suspected and no nodules are present.
Question – Hyperthyroidism workup
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)B. comprehensive urinalysis
C. thyroid peroxidase antibodies
D. thyrotropin receptor antibodies (TRAb)
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.
Why This Family Medicine Question Is Frequently Missed
- Examinees conflate general autoimmune thyroid antibodies (e.g., TPO) with the etiologic test for Graves (TRAb).- Overreliance on RAIU as the “only” definitive next step leads to overlooking TRAb’s high specificity and practicality.
- Failure to tailor the test choice to the clinical context (diffuse goiter, no nodules, no orbitopathy) where TRAb is efficient and cost-effective.
What the Distractors Indicate
| 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. |
High-Yield Pearl for Family Medicine Exam Prep
In overt thyrotoxicosis with diffuse goiter and no nodules, TRAb measurement is a guideline-endorsed, radiation-free first test to confirm Graves disease.
Core Learning Objectives
1. Select the most appropriate initial etiologic test for overt thyrotoxicosis based on clinical context (TRAb vs RAIU vs Doppler ultrasound).2. Differentiate the role of TRAb from other thyroid antibodies (e.g., TPO) in diagnosing Graves disease.
The “Test Trick” at Play
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.
Additional FM Practice Questions and Remediation for Thyrotoxicosis Workup
Family Medicine Practice Question 1 - Diffuse goiter, 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 DopplerB. RAIU scan
C. Thyroid peroxidase antibodies
D. Thyrotropin receptor antibodies (TRAb)
E. Serum thyroglobulin
Family Medicine Practice Question 2 - Painful thyroid, low uptake expected
A 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)B. TRAb
C. TPO antibodies
D. CT neck with contrast
Family Medicine Practice Question 3 - Pregnancy
A 10-week pregnant patient with overt thyrotoxicosis and diffuse goiter. Best test to confirm Graves etiology?
A. RAIUB. TRAb
C. TPO antibodies
D. MRI neck with gadolinium
Family Medicine Practice Question 4 - Nodular thyroid
A 63-year-old with thyrotoxicosis and palpable nodules. Next best test to determine etiology?
A. RAIU scanB. TRAb
C. TPO antibodies
D. ESR
Family Medicine Practice Question 5 - Amiodarone-associated
A 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 thyroidB. TRAb
C. TPO antibodies
D. Serum thyroglobulin alone
E. RAIU with I-123
Mini Case Discussion Prompt
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?
Mini-FAQ
- When should TRAb be ordered first?
Boards expect recognition that TRAb is first-line when Graves is suspected without nodules, including during pregnancy (ATA 2016; ETA 2018).
- When is RAIU preferred?
When nodularity is present or Graves vs thyroiditis is unclear and pregnancy is not a factor; RAIU provides functional differentiation.
- Do TPO antibodies diagnose Graves?
No. TPO indicates autoimmune thyroid disease broadly and lacks specificity for Graves; boards expect TRAb for Graves confirmation.
- Is thyroid ultrasound necessary in all hyperthyroid patients?
No. Reserve for suspected nodules or to assess vascularity in selected scenarios (e.g., amiodarone-induced thyrotoxicosis).
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