Initial Evaluation of Thyroid Function

Medical Experts

Contributor

Balogun

Kayode A. Balogun, PhD

Former Clinical Chemistry Fellow, Pathology, University of Utah School of Medicine

Contributor

Straseski

Joely A. Straseski, PhD, MS, MT(ASCP), DABCC, FAACC

Professor of Pathology (Clinical), University of Utah

Head of Clinical Operations for Clinical Chemistry, Toxicology, and Biochemical Genetics; Medical Director, Endocrinology; Co-Director, Automated Core Laboratory, ARUP Laboratories

Thyroid function tests are used in the initial evaluation of thyroid disease. The recommended first test is the measurement of thyroid-stimulating hormone (TSH, or thyrotropin), which is generally followed by a thyroxine (T4) test. In limited cases, triiodothyronine (T3) testing may be useful.

Quick Answers for Clinicians

When is triiodothyronine (T3) testing recommended?

Either total or free triiodothyronine (T3) tests are recommended in rare cases of suppressed serum thyroid-stimulating hormone (TSH) concentrations with normal free thyroxine (T4) concentrations (eg, in suspected T3 toxicosis, subclinical T3 hyperthyroidism, and rare pituitary conditions). Neither test is recommended for routine thyroid screening. Free T3 measurement may be used as a second-line test in the evaluation of individuals who are pregnant, receiving steroids, or who have dysalbuminemia. Free T3 tests should not be used in individuals with abnormal total T3 values. False-positive results may occur due to thyrotoxicosis or excess replacement therapy.

When is reverse triiodothyronine (T3) testing useful?

Reverse triiodothyronine (rT3) is a metabolite of thyroxine (T4), and its concentrations correlate with those of T4. There are no guidelines for rT3 testing, and its use in clinical practice varies widely. Although rT3 testing is not suitable for routine use, it does have limited applications. For example, rT3 testing may be used to direct T3 replacement therapy, distinguish nonthyroidal illness from central hypothyroidism, characterize rare conditions (eg, consumptive hypothyroidism, disorders associated with pathogenic MCT8 or SBP2 variants), or diagnose rT3 dominance (a controversial hypothesis in functional medicine).

Indications for Testing

Laboratory testing for thyroid disease may be used to screen for, diagnose, and manage:

This ARUP Consult topic focuses on the use and limitations of thyroid function tests; refer to the links above for the individual ARUP Consult topics that address testing specific to each condition.

Population Screening for Thyroid Disease

Population screening for thyroid dysfunction is not recommended for nonpregnant, asymptomatic adults. The American Thyroid Association (ATA) and American Association of Clinical Endocrinologists (AACE) recommend consideration of screening in patients >60 years of age, and consideration of “aggressive case finding” in individuals at increased risk of hypothyroidism (risk factors include history of autoimmune disease, head or neck irradiation, previous radioactive iodine therapy, family history of thyroid disease, and use of medications associated with thyroid dysfunction).

Laboratory Testing

Thyroid Function Tests

Thyroid function tests are recommended for the evaluation of suspected thyroid disease. Laboratory-specific reference intervals are recommended for thyroid tests because considerable variations exist among assays and among populations.

A TSH test is the recommended first-line test for suspected thyroid disease; if results are abnormal, the TSH test should be repeated along with a serum free T4 measurement. Of note, TSH concentrations may be abnormal due to nonthyroidal conditions. Measurement of total T4, rather than or in addition to measurement of free T4, may also be informative in some cases (eg, estrogen excess).

Total or free T3 measurement is useful to investigate certain cases of hyperthyroidism but is generally not useful in hypothyroidism.

Thyroid Hormone Concentrations in Thyroid Disease
Disease	TSH	Free T4	T3 (Free or Total)
Primary hypothyroidism^a	High	Low	Low or normal^b
Ablated thyroid	High	Low	Low or normal^b
Subclinical hypothyroidism^c	High	Normal	Normal
Hashimoto thyroiditis^a	High	Low	Low or normal^b
Transient (subacute) thyroiditis^d	High	Normal or low	Normal or high
T3 hypothyroidism	High	Normal	Low
Euthyroid sick syndrome^e	Normal or low	Normal or low	Low
Overt hyperthyroidism	Low (usually undetectable)	High	High
Subclinical hyperthyroidism	Low or undetectable	Normal	Normal
Graves disease^f	Low	High	High
Central hypothyroidism^g	Low	Low	Low
Severe illness	Low	Low	Not informative
Nonthyroidal illness syndrome	Normal or low	Normal or low	Low
TSH-secreting pituitary adenoma	Normal or high	High	High
^aAutoantibody testing may be used to distinguish between Hashimoto thyroiditis and other etiologies of hypothyroidism. See the ARUP Consult Autoimmune Thyroiditis topic for more information. ^bT3 testing is not generally useful in the investigation of hypothyroidism. ^cAdrenal insufficiency may result in a high TSH concentration that is reversed with glucocorticoid therapy. ^dAdditional findings in subacute thyroiditis may include high erythrocyte sedimentation rate, high C-reactive protein, and high Tg. ^eThe serum level of rT3 is increased in euthyroid sick syndrome, except in cases of renal failure. ^fAutoantibody testing may be used to distinguish between Graves disease and other etiologies of hyperthyroidism. See the ARUP Consult Autoimmune Thyroiditis topic for more information. ^gFree T4, not TSH, is recommended for diagnosis and treatment guidance in central hypothyroidism. AAFP, American Academy of Family Physicians; Tg, thyroglobulin; rT3, reverse T3; Sources: Garber, 2012; Kravets, 2016; Ross, 2016