Hyperthyroidism Workup

Author: Stephanie L Lee, MD, PhD; Chief Editor: George T Griffing, MD more...

Updated: Oct 27, 2011

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Approach Considerations
TSH and Thyroid Hormone Levels
Other Laboratory Tests
Scintigraphy
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Approach Considerations

The most reliable screening measure of thyroid function is TSH level. TSH levels usually are suppressed to immeasurable levels (< 0.05 µIU/mL) in thyrotoxicosis. Third-generation TSH assays are recommended for screening purposes.

The most specific autoantibody test for autoimmune thyroiditis is an enzyme-linked immunosorbent assay (ELISA) test for anti-TPO antibody.

Hyperthyroidism in older patients often presents with atrial arrhythmias or CHF. Electrocardiography is recommended if an irregular heart rate or CHF is noted upon examination.

TSH and Thyroid Hormone Levels

Although measurement of the TSH level is the most reliable screening method for assessing thyroid function, the degree of thyrotoxicosis cannot be estimated easily in this way; thyrotoxicosis must instead be measured using an assay of thyroid hormone levels in the plasma. Thyroid hormone circulates as T₃ and T₄, with 99% bound to protein.

Only the free, unbound thyroid hormone is biologically active. T₃ is 20-100 times more biologically active than T₄. Of patients with thyrotoxicosis, 5% have only elevated T₃ levels. Therefore, measuring FT₄ (and FT₃, if FT₄ levels are normal) is recommended in patients with suspected thyrotoxicosis when TSH is low.

Many laboratories do not measure free FT₄ directly, instead using a calculation to estimate the FT₄ levels. The free thyroxine index (FTI) is equal to total T₄ multiplied by the correction for thyroid hormone binding, such as the thyroid hormone ̶ binding ratio (THBR) or T₃ resin uptake [T₃ RU]). A similar calculation can be used with total T₃.

Subclinical hyperthyroidism is defined as a suppressed TSH level (< 0.5 μU/mL in many laboratories) in combination with serum concentrations of T₃ and T₄that are within the reference range.

Other Laboratory Tests

As previously mentioned, the most specific autoantibody test for autoimmune thyroiditis is an ELISA test for anti-TPO antibody. The titers usually are significantly elevated in the most common type of hyperthyroidism, Graves thyrotoxicosis, and usually are low or absent in toxic multinodular goiter and toxic adenoma. A significant number of healthy people without active thyroid disease have mildly positive TPO antibodies; thus, the test should not be performed for screening purposes.

TSI, if elevated, helps to establish the diagnosis of Graves disease. A positive anti-TG antibody test does not predict the development of thyroid dysfunction, so the test should not be used.

Scintigraphy

If the etiology of thyrotoxicosis is not clear after physical examination and other laboratory tests, it can be confirmed by a iodine-123 (¹²³ I) uptake, as in the images below. Values are elevated in patients with Graves disease and toxic multinodular goiters.¹²³ I and technetium-99m (^99m Tc) can be used for thyroid scanning, which provides anatomic information on the type of goiter (eg, diffuse vs nodular). Scans essentially are pictures of the thyroid and do not necessarily confirm or refute the presence of hyperthyroidism per se; only¹²³ I uptake provides information in this area.

Graves disease is associated with diffuse enlargement of both thyroid lobes, with an elevated uptake. A toxic adenoma demonstrates a solitary hot nodule with suppression of function in the surrounding normal thyroid tissue. A toxic multinodular goiter demonstrates an enlarged thyroid with multiple nodules and areas of increased and decreased isotope uptake. (See the first 2 images below.) Subacute thyroiditis usually demonstrates very low¹²³ I isotope uptake. (See the third image below.)

Iodine 123 (123I) nuclear scintigraphy: 123I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).

Scan in a patient with a toxic multinodular goiter. The 5-hour iodine uptake was elevated at 28%. Note the multiple foci of variably increased tracer uptake.

Absence of iodine 123 (123I) radioactive iodine uptake in a patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T4), 21.2 mcg/dL (reference range, 4.5-11); total triiodothyronine (T3), 213 ng/dL (reference range, 90-180); T3-to-T4 ratio, 10; and erythrocyte sedimentation rate (ESR), 10 mm/h. The absence of thyroid uptake, the low T3-to-T4 ratio, and the low ESR confirm the diagnosis of subacute painless thyroiditis.

If a dominant nodule is found upon examination of a patient with thyrotoxicosis, obtain an¹²³ I thyroid scan to assure that the dominant nodule is functioning. If the nodule is cold, perform a biopsy on the nodule by fine-needle aspiration to exclude concomitant malignancy.

Proceed to Treatment & Management

Contributor Information and Disclosures

Author

Stephanie L Lee, MD, PhD Associate Professor, Department of Medicine, Boston University School of Medicine; Director of Thyroid Health Center, Associate Chief, Section of Endocrinology, Diabetes and Nutrition, Boston Medical Center; Fellow, Association of Clinical Endocrinology

Stephanie L Lee, MD, PhD is a member of the following medical societies: American College of Endocrinology, American Thyroid Association, and Endocrine Society

Disclosure: Nothing to disclose.

Coauthor(s)

Sonia Ananthakrishnan, MD Assistant Professor of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Medical Center

Disclosure: Nothing to disclose.

Specialty Editor Board

Frederick H Ziel, MD Associate Professor of Medicine, University of California, Los Angeles, David Geffen School of Medicine; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

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

Disclosure: Medscape Salary Employment

Chief Editor

George T Griffing, MD Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

References

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[Best Evidence] Worni M, Schudel HH, Seifert E, Inglin R, Hagemann M, Vorburger SA, et al. Randomized controlled trial on single dose steroid before thyroidectomy for benign disease to improve postoperative nausea, pain, and vocal function. Ann Surg. Dec 2008;248(6):1060-6. [Medline].
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Severe proptosis and eyelid retraction from thyroid-related orbitopathy. This patient also had optic nerve dysfunction from thyroid related orbitopathy.

Color flow ultrasonogram in a patient with Graves disease. Generalized hypervascularity is visible throughout the gland, which often can be heard as a hum or bruit with a stethoscope.

Absence of iodine 123 (¹²³I) radioactive iodine uptake in a patient with thyrotoxicosis and subacute painless or lymphocytic thyroiditis. Laboratory studies at the time of the scan demonstrated the following: thyroid-stimulating hormone (TSH), less than 0.06 mIU/mL; total thyroxine (T₄), 21.2 mcg/dL (reference range, 4.5-11); total triiodothyronine (T₃), 213 ng/dL (reference range, 90-180); T₃-to-T₄ ratio, 10; and erythrocyte sedimentation rate (ESR), 10 mm/h. The absence of thyroid uptake, the low T₃-to-T₄ ratio, and the low ESR confirm the diagnosis of subacute painless thyroiditis.

Three multinuclear giant cell granulomas observed in a fine-needle aspiration biopsy of the thyroid from a patient with thyrotoxicosis from subacute painful or granulomatous thyroiditis.

Scan in a patient with a toxic multinodular goiter. The 5-hour iodine uptake was elevated at 28%. Note the multiple foci of variably increased tracer uptake.

Iodine 123 (¹²³I) nuclear scintigraphy: ¹²³I scans of a normal thyroid gland (A) and common hyperthyroid conditions with elevated radioiodine uptake, including Graves disease (B), toxic multinodular goiter (C), and toxic adenoma (D).

Table 1. Common, Less Common, and Uncommon Forms of Thyrotoxicosis and Hyperthyroidism

Table 1. Common, Less Common, and Uncommon Forms of Thyrotoxicosis and Hyperthyroidism

Common Forms (85-90% of cases)	Radioactive iodine uptake over neck
Diffuse toxic goiter (Graves disease)	Increased
Toxic multinodular goiter (Plummer disease)	Increased
Thyrotoxic phase of subacute thyroiditis	Decreased
Toxic adenoma	Increased
Less Common Forms
Iodide-induced thyrotoxicosis	Variable
Thyrotoxicosis factitia	Decreased
Uncommon Forms
Pituitary tumors producing thyroid-stimulating hormone	Increased
Excess human chorionic gonadotropin (molar pregnancy/choriocarcinoma)	Increased
Pituitary resistance to thyroid hormone	Increased
Metastatic thyroid carcinoma	Decreased
Struma ovarii with thyrotoxicosis	Decreased

View Table List

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