Laboratory Studies

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

With the exception of thyrotropin-induced hyperthyroidism, subnormal or suppressed thyrotropin 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 thyrotropin, 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 thyrotropin-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 thyrotropin 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.

Thyrotropin-releasing hormone testing has largely been replaced by third-generation thyrotropin assays.

A high titer of serum antibodies to collagen XIII is associated with active Graves ophthalmopathy.^[42]

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.^[3]

Ultrasounds with color-Doppler evaluation have been found to be cost-effective in hyperthyroid patients.^{[31, 43]}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.^[44]

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.

Treatment & Management

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Media Gallery

Pathophysiologic mechanisms of Graves disease relating thyroid-stimulating immunoglobulins to hyperthyroidism and ophthalmopathy. T4 is levothyroxine. T3 is triiodothyronine.
Graves disease. Varying degrees of manifestations of Graves ophthalmopathy.

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Author

Sai-Ching Jim Yeung, MD, PhD, FACP Professor of Medicine, Department of Emergency Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center

Sai-Ching Jim Yeung, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Medical Association, American Thyroid Association, Endocrine Society

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Celgene, Inc.<br/>Received research grant from: DepoMed and Bristol-Myer-Squibb.

Coauthor(s)

Mouhammed Amir Habra, MD Endocrine Fellow, Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center

Mouhammed Amir Habra, MD is a member of the following medical societies: American College of Physicians, American Thyroid Association, Endocrine Society

Disclosure: Nothing to disclose.

Alice Cua Chiu, MD Associate Affiliate, Department of Internal Medicine, Division of Endocrinology, Bayshore Medical Center

Alice Cua Chiu, MD is a member of the following medical societies: American Medical Association, Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kent Wehmeier, MD Professor, Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, St Louis University School of Medicine

Kent Wehmeier, MD is a member of the following medical societies: American Society of Hypertension, Endocrine Society, International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP (Retired) Professor, Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Steven R Gambert, MD Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Physician Leadership, American College of Physicians, American Geriatrics Society, Endocrine Society, Gerontological Society of America, Association of Professors of Medicine

Disclosure: Nothing to disclose.