Diffuse Toxic Goiter (Graves Disease) Workup

Updated: Dec 10, 2020
  • Author: Bernard Corenblum, MD, FRCPC; Chief Editor: George T Griffing, MD  more...
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Approach Considerations

Acording to the American Thyroid Association guidelines for diagnosis and management of hyperthyroidism, serum thyroid-stimulating hormone (TSH) should be the initial biochemical evaluation, because it has the highest sensitivity and specificity in the diagnosis of thyroid disorders. [1]  If the diagnosis is not apparent from the clinical presentation and serum TSH measurement, further diagnostic tests should be selected based on available expertise and resources and can include the following:

  • Measurement of TSH-receptor antibodies  (TRAb)
  • Determination of the radioactive iodine uptake (RAIU)
  • Measurement of thyroidal blood flow on ultrasonography
  • Thyroid scan (technetium-99m or iodine-123) 

The presence of ophthalmopathy indicates the diagnosis for Graves disease, and no further diagnostic testing is needed regarding the cause of the hyperthyroidism. If confirmation of oculopathy is needed, then orbital computed tomography (CT) scanning or magnetic resonance imaging (MRI) may be performed. 

Diffuse toxic goiter typically demonstrates a suppressed serum TSH level, elevated serum free thyroxine level (or T3 if needed), elevated titers of TRab, or elevated radioiodine uptake.


Laboratory Studies

TSH and thyroid hormone levels

Serum thyroid-stimulating hormone (TSH) (sensitive or third-generation assay) with levels suppressed below normal indicates the need for more tests. Normal serum TSH levels rule out Graves disease.

For serum free thyroxine (T4), if levels are elevated, then hyperthyroidism is diagnosed. Levels will be in the normal range in about 5% of cases. If free thyroxine is normal, then obtain total or free serum triiodothyronine (T3) levels. If the levels are elevated, then hyperthyroidism is diagnosed. If the levels are normal, then subclinical hyperthyroidism is present.

Measurement of serum anti-TSH receptor antibodies can be obtained. These antibodies are present in more than 90% of cases of diffuse toxic goiter, depending on the assay. Concomitant presence of Hashimoto thyroiditis may be detected by serum antithyroid antibodies (anti-TPO or thyroperoxidase).

Drugs that may alter T4 laboratory results include anabolic steroids, androgens, estrogens, heparin, iodine, phenytoin, rifampin, salicylates, and thyroxine/triiodothyronine.


Imaging Studies

Radioactive iodine uptake (RAIU) test

Thyroid radioactive iodine uptake test results are as follows [2]

  • Diffuse toxic goiter (Graves disease): Diffuse high radioiodine uptake. 
  • Toxic multinodular goiter: Normal or high radioiodine uptake with an asymmetrical pattern 
  • Toxic adenoma: Normal or high radioiodine uptake with a localized and focal pattern 
  • Thyroiditis: Low radioiodine uptake
  • Thyrotoxicosis from extrathyroidal sources of thyroid hormone: Very low uptake 

NOTE: This test is contraindicated in women who are pregnant or breastfeeding.


Thyroid ultrasonography and thyroid RAIU have similar sensitivity for the diagnosis of Graves disease. Advantages of ultrasonography are the absence of exposure to ionizing radiation, and a higher accuracy in the detection of thyroid nodules and lower cost than with RAIU. [2]  If Doppler ultrasonography is used to assess vascularity, it accurately distinguishes diffuse toxic goiter (increased blood flow, diffusely enlarged hypoechogenic) from thyroiditis (decreased blood flow), the most common clinical problem in the differential diagnosis of hyperthyroidism. [10, 11]


Other Tests

Testing for comorbidities

Electrocardiography (ECG) should be performed if arrhythmia is suspected; liver function tests may be indicated. If clinical suspicion exists, screen for adrenal insufficiency, type 1 diabetes, gonadal failure, and/or other autoimmune disease (eg, pernicious anemia, rheumatoid arthritis, immune thrombocytopenic purpura). Concomitant Hashimoto thyroiditis may have an effect on spontaneous resolution or progression to a hypothyroid state.