Diffuse Toxic Goiter (Graves Disease) Workup

Updated: Jul 27, 2015
  • Author: Bernard Corenblum, MD, FRCPC; Chief Editor: George T Griffing, MD  more...
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Laboratory Studies

If hyperthyroidism due to diffuse toxic goiter is suspected after history and physical examination, the following should be performed:

  • Serum TSH (sensitive or third-generation assay): Levels suppressed below normal indicate the need for more tests. Normal serum TSH level rules out this diagnosis.

  • Serum free thyroxin (T4), or equivalent test, that compensates for any changes in thyroid-binding globulin. If levels are elevated, then hyperthyroidism is diagnosed. Levels will be in the normal range in about 5% of cases.

  • If free thyroxin is normal, then obtain total or free serum triiodothyronine (T3) level. If levels are elevated, then hyperthyroidism is diagnosed. If levels are normal, then subclinical hyperthyroidism is present.

  • The presence of ophthalmopathy indicates the diagnosis, and no more diagnostic testing is needed regarding the cause of the hyperthyroidism.

  • Serum anti-TSH receptor antibodies measurements can be obtained. These antibodies are present in more than 90% of cases of diffuse toxic goiter, depending on the assay.

  • An alternative test is radioiodine uptake. It will separate diffuse toxic goiter (elevated or normal uptake) from the hyperthyroid phase of thyroiditis (suppressed uptake). If the hyperthyroid symptoms have been present for more than 4 months, then thyroiditis is not the cause. This test is contraindicated in women who are pregnant or breastfeeding.

  • An elevated or normal uptake may be found with a single nodular goiter and a multinodular goiter. These may be separated from diffuse toxic goiter by the absence of anti-TSH receptor antibodies, clinical examination, or thyroid scan (technetium-99m or I-123) or ultrasonography.

  • Concomitant presence of Hashimoto thyroiditis may be detected by serum antithyroid antibodies (anti-TPO or thyroperoxidase).

  • If confirmation of oculopathy is needed, then orbital CT or MRI may be performed.

Diffuse toxic goiter would have a suppressed serum TSH level, elevated serum free thyroxin level (or T3 if needed), elevated titer of anti-TSH receptor antibodies, or elevated radioiodine uptake. No further testing is needed.

Consideration of complications: ECG should be performed if arrhythmia is suspected; liver function tests may be indicated.

Consideration of associated disorders: If clinical suspicion, screen for adrenal insufficiency, type 1 diabetes, gonadal failure, 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.

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


Imaging Studies

Radiological studies are useful. The radioiodine uptake is elevated or normal with diffuse toxic goiter, functioning nodule, and multinodular goiter. It is low with thyroiditis (all causes), exogenous thyroid administration, and ectopic sources such as struma ovarii.

The thyroid scan is useful but more expensive and with greater radiation exposure. It shows a diffuse uptake with diffuse toxic goiter, a single area of uptake over a functioning nodule, and several areas of uptake over a multinodular goiter. It is best used if nodularity is suspected.

Ultrasound is a sensitive and inexpensive test, without radiation exposure, if Doppler is used to assess vascularity. The vascularity accurately distinguishes diffuse toxic goiter from thyroiditis, the most common clinical problem in the differential diagnosis of hyperthyroidism. [1]