Graves Disease Workup

Updated: Jan 04, 2023
  • Author: Sai-Ching Jim Yeung, MD, PhD, FACP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
  • Print

Laboratory Studies

Ultrasensitive (third-generation) TSH assays remain the best screening test for thyroid disorders.

  • With the exception of TSH-induced hyperthyroidism, subnormal or suppressed TSH levels are seen in most patients with thyrotoxicosis.

  • Free T4 levels or the free T4 index is usually elevated, as is the free T3 level or free T3 index. Subclinical hyperthyroidism, defined as a free T4 or free T3 level within the reference range with suppressed TSH, also can be seen.

  • On occasion, only the free T3 level is elevated, a syndrome known as T3 toxicosis. This may be associated with toxic nodular goiter or the ingestion of T3. Elevated T3 levels are often seen in early phase Graves disease as well.

  • Assays for TSH-receptor antibodies (particularly TSIs) almost always are positive.

  • Detection of TSIs is diagnostic for Graves disease.

  • The presence of TSIs is particularly useful in reaching the diagnosis in pregnant women, in whom the use of radioisotopes is contraindicated.

  • Other markers of thyroid autoimmunity, such as antithyroglobulin antibodies or antithyroidal peroxidase antibodies, are usually present.

  • Other autoantibodies that may be present include TSH receptor–blocking antibodies and anti–sodium-iodide symporter antibody.

  • The presence of these antibodies supports the diagnosis of an autoimmune thyroid disease.

Liver function test results should be obtained to monitor for liver toxicity caused by thioamides (antithyroid medications).

A CBC with differential should be obtained at baseline and with the development of fever or symptoms of infection. Graves disease may be associated with normocytic anemia, low-normal to slightly depressed total WBC count with relative lymphocytosis and monocytosis, and low-normal to slightly depressed platelet count. Thioamides may rarely cause severe hematologic side effects, but routine screening for these rare events is not cost-effective.

Investigation of gynecomastia associated with Graves disease may reveal increased sex hormone–binding globulin levels and decreased free testosterone levels.

Graves disease may worsen diabetes control and may be reflected by an increase in hemoglobin A1C in diabetic patients.

A fasting lipid profile may show decreased total cholesterol levels and decreased triglyceride levels.

TSH-releasing hormone testing has largely been replaced by third-generation TSH assays.

A high titer of serum antibodies to collagen XIII is associated with active Graves ophthalmopathy. [52]


Imaging Studies

Radioactive iodine scanning and measurements of iodine uptake are useful in differentiating the causes of hyperthyroidism. In Graves disease, the radioactive iodine uptake is increased, and the uptake is diffusely distributed over the entire gland. [4]

Ultrasounds with color-Doppler evaluation have been found to be cost-effective in hyperthyroid patients. [41, 53] A prospective trial showed that thyroid ultrasound findings are predictive of radioiodine treatment outcome, and, in patients with Graves disease, normoechogenic and large glands are associated with increased radioresistance. [54]

Computed tomography scanning or magnetic resonance imaging (of the orbits) may be necessary in the evaluation of proptosis. If routinely performed, most patients have evidence of ophthalmopathy, such as an increased volume of extraocular muscles and/or retrobulbar connective tissue. These techniques are useful to monitor changes over time or to ascertain the effects of treatment. Careful monitoring is required after using iodinated contrast agents as they may affect ongoing treatment plans.


Histologic Findings

In select cases in which thyroidectomy was performed for the treatment of severe hyperthyroidism, the thyroid glands from patients with Graves disease show lymphocytic infiltrates and follicular hypertrophy, with little colloid present.