Interpreting Thyroid Function Tests

Educational Objectives

The goal of this program is to improve management of thyroid disorders. After hearing and assimilating this program, the clinician will be better able to:

1. Interpret laboratory findings in patients with a suspected thyroid disorder.

2. Recognize abnormal patterns in results of thyroid function testing.

Summary

Thyroid function: hypothalamus secretes thyroid-releasing hormone (TRH), which stimulates pituitary gland to release thyrotropin (TSH); TSH causes enlargement of thyroid gland and increases production of thyroid hormones; active thyroid hormones — levorotatory thyroxine (T4; long acting [half-life 10 days]); triiodothyronine (T3; short acting); function as stimulant; 3 main deiodinases affected by disease

Laboratory testing: suspected hypothyroidism — TSH usually sufficient, unless pituitary or hypothalamic problem suspected (eg, closed head injury, hypogonadism [check free T4]); thyroid peroxidase (TPO) antibody useful for ruling out Hashimoto thyroiditis (most common cause of hypothyroidism); total T3; suspected hyperthyroidism — TSH; free T4; total T3; free T3 assays not adequate because of high rate of laboratory error; total thyroid hormone levels significantly influenced by protein binding (eg, total T3 may appear higher than actual free T3 level in, eg, women on estrogen therapy with higher binding protein); suspected Graves disease — thyroid-stimulating immunoglobulin (TSI); signs include restlessness, proptosis, goiter, and bruit (highly specific)

Expected laboratory findings: hypothyroidism — elevated TSH; low free T4; low total T3; TPO antibodies can be positive or negative; hyperthyroidism — suppressed TSH (often unmeasurable); elevated free T4 and total T3; Graves disease — high T3; normal free T4; TSI typically positive

Causes of Abnormal Thyroid Function Testing

Low TSH with elevated free T4 and T3: common — primary hyperthyroidism; nonthyroidal illness syndrome (NTIS; free T4 elevated or normal with low T3); low to unmeasurable uptake of radioactive iodine — thyroiditis (eg, subacute thyroiditis with painful thyroid); inflammation during early Hashimoto disease (“hashitoxicosis”) causes excess release of thyroid hormone; granulomatous thyroiditis; postpartum thyroiditis; rare — gestational thyrotoxicosis; hydatidiform mole; familial gestational hyperthyroidism; activating TSH receptor mutations

Low TSH with normal free T4 and T3: common — subclinical hyperthyroidism; thyroxine ingestion; rare — high-dose glucocorticoids; dopamine; dobutamine; NTIS

Low or normal TSH with low free T4 and T3: common — NTIS; recent treatment for hyperthyroidism; rare — secondary hypothyroidism in, eg, patient who underwent pituitary surgery or had head injury; congenital deficiencies

Elevated TSH with low free T4 and T3: hypothyroidism; history of external-beam radiotherapy (EBRT) in patients with, eg, head and neck squamous cell cancer or lymphoma; amiodarone; lithium; interferons; interleukin-2; iodine deficiency or excess; amyloidosis; Reidel thyroiditis; congenital problems with or without presence of thyroid tissue

Elevated TSH with normal free T4 and T3: subclinical hypothyroidism; interfering antibodies; drugs; intermittent T4 therapy for hypothyroidism (in, eg, noncompliant patients); congenital problems

Normal or elevated TSH with elevated free T4 and T3: rare; interfering antibodies; familial dysalbuminemic hyperthyroxinemia (caused by high levels of protein binding to T4); amiodarone; resistance to thyroid hormone; TSH-secreting pituitary tumor (rare); psychiatric illness

Nonthyroidal illness syndrome: illness causes changes in endocrine systems (including thyroid axis); unknown pre-existing disease can complicate management; treatment of severe illness can change thyroid function and laboratory test results (important to decide whether intervention needed); monitoring and repeat testing should be continued after illness resolves; workup — TSH alone insufficient; important to check free T4; if TSH low, measure total T3 to determine whether patient has hyperthyroidism or NTIS; to distinguish between NTIS and central hypothyroidism (in, eg, patients with low TSH, free T4, and T3) consider pituitary gland or hypothalamus dysfunction and check reverse T3 level; thyroid antibodies can help to detect pre-existing disease; patients with TSH levels 0.05 to 0.30 mIU/L likely to be euthyroid after recovery from illness; ≈75% of patients with TSH <0.01 mIU/L have hyperthyroidism; most patients with TSH >20 mIU/L have hypothyroidism; summary — common in hospitalized patients (particularly critically ill patients); pathogenesis complicated; determining whether abnormalities caused by intrinsic thyroid disease or NTIS difficult, and often cannot be clarified until patient recovers from illness; data do not support treatment of NTIS; do not order thyroid function testing unless thyroid disease suspected

Questions and answers: guidelines — treatment not necessary in older patients with TSH ≤10 mIU/L; use lower TSH threshold for treating younger patients; consider offering patient trial of thyroid hormone (stop or continue based on patient’s response); decision to treat — treat patients with symptoms suggestive of hypothyroidism to normalize TSH, then continue or stop treatment based on response; range of normal levels of thyroid hormone — wide; older population studies showed that individuals maintained narrow range of thyroid hormone levels (suggests that “normal TSH level” may vary among individuals [clinicians should listen to patients with hypothyroidism and consider symptoms])

Desiccated thyroid products (eg, Armour Thyroid, Nature-Throid, NP Thyroid): made from purified porcine thyroid glands; compared with humans, pigs have much higher levels of T3 than T4 in thyroid glands; be cautious about use of desiccated products in high-risk populations (eg, elderly patients, patients with history of atrial fibrillation, patients with anxiety) because high dose of short-acting stimulant can trigger problems; reasonable for normalizing TSH, or when using separate T3 or liothyronine (Cytomel) along with T4; should not be used as first-line treatment

Generic thyroid hormones: pharmacies often switch manufacturers, and this can cause changes in TSH; thyroid hormone difficult to absorb (only 50%-60% of tablet absorbed), and absorption can be affected by, eg, changes in gastric motility, bacterial overgrowth, inflammation; manufacturers add fillers than can affect absorption; patients with narrow range of TSH (eg, patients with thyroid cancer) should track manufacturer of generic product (check TSH level 6 wk later to determine whether change in dose necessary)

Complementary and alternative approaches: discourage use of high-dose iodine; monitoring and adjusting thyroid hormone important

Readings

Beckett GJ, Toft AD: First-line thyroid function tests -- TSH alone is not enough. Clin Endocrinol (Oxf). 2003 Jan;58(1):20-1; Boelen A: Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev. 2011 Oct;32(5):670-93; De Vries EM et al: The molecular basis of the non-thyroidal illness syndrome. J Endocrinol. 2015 Jun;225(3):R67-81; Eales M: Thyroid function tests. Thyroid function testing means different things to different people. BMJ. 2000 Oct 28;321(7268):1081-2; Hennemann G et al: Causes and effects of the low T3 syndrome during caloric deprivation and non-thyroidal illness: an overview. Acta Med Austriaca. 1988;15 Suppl 1:42-5; Khatami Z et al: Borderline thyroid function tests: so easy to look at, so hard to define. Ann Clin Biochem. 2006 Jan;43(Pt 1):77-9; Price A, Weetman AP: Thyroid function tests. Thyroid stimulating hormone outside the normal range has important implications. BMJ. 2000 Oct 28;321(7268):1080; Supit EJ, Peiris AN: Interpretation of laboratory thyroid function tests for the primary care physician. South Med J. 2002 May;95(5):481-5.

Disclosures

 For this program, the following has been disclosed: Dr. Edwards reported nothing to disclose. The planning committee reported nothing to disclose.

Acknowledgements

Dr. Edwards was recorded in Orlando, FL, at Current Challenges in Primary Care 2019, presented June 20-21, 2019, by the University of Florida College of Medicine. Please visit cme.ufl.edu for information about upcoming events from this sponsor. The Audio Digest Foundation thanks the speakers and sponsors for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

FP674701

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.