Before discussing thyroid dysfunction and testing, let’s briefly review the relevant thyroid physiology.
TSH is produced by the pituitary gland, and its primary action is on the thyroid gland to stimulate the secretion of T3 and T4. The production of TSH is under negative feedback by the serum concentrations of both T3 and T4; this regulatory mechanism is exquisitely sensitive to changes in levels of T3 and T4. T3 is the metabolically active hormone. T4 is the prohormone and has minimal metabolic activity. The thyroid gland stores about a 3 month supply of these thyroid hormones. Essentially 100% of T4 is synthesized in the thyroid, while only about 20% of T3 is synthesized in the thyroid. The remainder of T3 is synthesized from T4 in peripheral organs (liver, kidneys, etc.) by deiodination, a process that is under both positive and negative feedback by various stimuli. Both T3 and T4 are >99% protein bound (primarily to TBG, thyronine-binding globulin), and it is only the <1% of free hormone that have activity.
Thyroid dysfunction comprises a host of disease states frequently encountered in the Emergency Department. Ranging from asymptomatic to life-threatening, these conditions are notoriously nonspecific in their presentation. For these reasons, we often place some version of thyroid disease on the differential, usually smoldering somewhere halfway down the list. In fact, one of my colleagues in medical school took advantage of this by keeping the canned response of, “this could represent an atypical presentation of thyroid disease”, which he would lob out as a hail mary when being pimped and finding that the (more) correct answer had evaded him. Although thyroid dysfunction may be difficult to recognize clinically, especially in early disease states, thankfully several laboratory assays are available in the ED.
The first and best test for evaluating thyroid function. It is the most sensitive test for thyroid dysfunction, such that a normal TSH value rules out hypothyroidism and hyperthyroidism except under very rare circumstances. As TSH levels are under negative feedback, they will typically be inversely correlated with overall thyroid activity (exception: central hypothyroidism or hyperthyroidism).
Unfortunately, this test may not be readily available in many emergency departments. In most cases, free T3 and free T4 levels will be concordant with each other and with the overall thyroid activity. Thus, routine free T3 testing is not necessary. However, free T3 testing (in addition to TSH and free T4) is indicated in cases where the provider has a high clinical suspicion for hyperthyroidism. The following scenarios illustrate examples of discordant free T3 and free T4:
This test is available in most emergency departments. If the TSH is abnormal, this is the best next step to evaluate for suspected hypothyroidism and hyperthyroidism. If time is of the essence (isn’t it always?), send a free T4 level with your initial TSH. In most instances, free T4 correlates with overall thyroid activity.
Total T4, Total T3
This tests for all T4 or T3, including protein-bound and metabolically inactive hormone. These levels can be altered by anything that changes the concentration of TBG. A brief, uncomprehensive list of things that affect these tests: liver disease, nutrition status, severe systemic illness of any kind, pregnancy, steroids, lasix, heparin, aspirin, NSAIDs. (1) Verdict: Total T4 and Total T3 are unreliable in the ED population.
This algorithm offers a simplified and systematic approach to the interpretation of these tests. While not intended to be comprehensive, it hopefully adds some insight into the diagnosis of the more common disease states encountered in the ED.
Lastly, let's cover a few salient points on the more obscure thyroid conditions. While these conditions may not give us the same excitement as the seizing patient in a thyroid storm, it is no less our responsibility as emergency physicians to understand the appropriate management and disposition for these patients.
a variety of hyperthyroidism where free T4 is low or normal, TSH will be low/undetectable and free T3 will be elevated
- Especially prominent in the elderly. Represents 5% of all hyperthyroidism. May be associated with typical hyperthyroidism symptoms, but can be severe enough to cause thyroid storm.
- Ingestion. Levothyroxine (Synthroid) is synthesized T4. TSH will be low, free T4 will be high, free T3 may be low or normal.
- Direct insult to the thyroid gland (thyroiditis, trauma). Because the thyroid gland stores a 3 month supply of thyroid hormone, a direct insult can release T4 in excess to T3. Free T4 will be high, free T3 may be low or normal.
High TSH, Normal T4
- There is some controversy as to whether these patients may benefit from levothyroxine. (2)
- Studies have shown these patients are at increased risk of developing overt hypothyroidism. (3)
- These patients do not have normal thyroid test results and need outpatient follow-up and repeat thyroid function testing.
Euthymic Sick Syndrome
Low TSH/T4/T3 in the setting of critical illness
- Portends mortality.
- Studies have not demonstrated a benefit to levothyroxine in these patients. (4)
Low TSH, Normal T3/T4
- Increased risk for mortality, CAD, cardiac events, atrial fibrillation
- Studies have shown these patients are at increased risk of developing overt hyperthyroidism. (5)
- These patients do not have normal thyroid test results and need outpatient follow-up.
- Appropriate follow-up for repeat testing is 2-6 weeks in high-risk individuals and 3-6 months for low-risk individuals
Content by Jim Makinen, MD
Editing and post by Ryan LaFollette, MD
- Pimentel, Laura, and Karen N. Hansen. “Thyroid Disease in the Emergency Department: A Clinical and Laboratory Review.” The Journal of Emergency Medicine, vol. 28, no. 2, 2005, pp. 201–209., doi:10.1016/j.jemermed.2004.08.020.
- Stott, David J., et al. “Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.” New England Journal of Medicine, vol. 376, no. 26, 2017, pp. 2534-2544., doi:10.1056/neimoa1603825
- Jonklaas, Jacqueline, et al. “Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement.” Thyroid, vol. 24, no. 12, 2014, pp. 1670–1751., doi:10.1089/thy.2014.0028.
- Lee, Sun, and Alan P. Farwell. “Euthyroid Sick Syndrome.” Comprehensive Physiology, 2016, pp. 1071–1080., doi:10.1002/cphy.c150017.
- Ross, Douglas S., et al. “2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis.” Thyroid, vol. 26, no. 10, 2016, pp. 1343–1421., doi:10.1089/thy.2016.0229.
- Walls, Ron M., et al. “Rosen's Emergency Medicine: Concepts and Clinical Practice.” Rosen's Emergency Medicine: Concepts and Clinical Practice, edited by Robert S. Hockberger, 9th ed., vol. 2, Elsevier, 2018, pp. 1557–1567.