Thyroid Function Cascade, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
This test utilizes a cascaded testing procedure to efficiently evaluate and monitor functional thyroid status.
The cascade begins with thyroid-stimulating hormone (TSH) as a screening assay. In patients with an intact pituitary-thyroid axis, TSH provides a physiologic indicator of the functional level of thyroid hormone activity. Increased TSH indicates inadequate thyroid hormone, and suppressed TSH indicates excess thyroid hormone.
Transient TSH abnormalities may be found in seriously ill, hospitalized patients, so this is not the ideal setting to assess thyroid function. However, even in these patients, TSH works better than total thyroxine (an alternative screening test).
When TSH is normal, no additional testing will be necessary. However, when the TSH result is abnormal, appropriate follow-up tests will automatically be performed.
If TSH is <0.3 mIU/L or >4.2 mIU/L, free thyroxine (FT4) is performed. The supplemental measurement of FT4 in patients with abnormal TSH measurements allows one to better assess the severity of the changes.
Serum triiodothyronine (T3) levels often are depressed in sick and hospitalized patients, caused in part by the biochemical shift to the production of reverse T3. Therefore, T3 generally is not a reliable predictor of hypothyroidism. However, in a small subset of hyperthyroid patients, hyperthyroidism may be caused by overproduction of T3 (T3 toxicosis). To help diagnose and monitor this subgroup, T3 is measured on all specimens with suppressed TSH and normal FT4 concentrations.
Detectable concentrations of antithyroperoxidase (anti-TPO) antibodies are observed in patients with autoimmune thyroiditis and may cause the destruction of thyroid tissue, resulting in the eventual hypothyroidism. Anti-TPO antibodies are measured in all specimens with elevated TSH concentrations.
See Thyroid Function Ordering Algorithm in Special Instructions.
Screening for a diagnosis of thyroid disease
In primary hypothyroidism, thyroid-stimulating hormone (TSH) levels will be elevated. In primary hyperthyroidism, TSH levels will be low.
The ability to quantitate circulating levels of TSH is important in evaluating thyroid function. It is especially useful in the differential diagnosis of primary (thyroid) from secondary (pituitary) and tertiary (hypothalamus) hypothyroidism. In primary hypothyroidism, TSH levels are significantly elevated, while in secondary and tertiary hypothyroidism, TSH levels are low or normal.
Elevated or low TSH in the context of normal free thyroxine is often referred to as subclinical hypo- or hyperthyroidism, respectively.
Thyrotropin-releasing hormone (TRH) stimulation differentiates all types of hypothyroidism by observing the change in patient TSH levels in response to TRH. Typically, the TSH response to TRH stimulation is exaggerated in cases of primary hypothyroidism, absent in secondary hypothyroidism, and delayed in tertiary hypothyroidism. Most individuals with primary hyperthyroidism have TSH suppression and do not respond to TRH stimulation test with an increase in TSH over their basal value.
Sick, hospitalized patients may have falsely low or transiently elevated TSH.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
In patients receiving therapy with high biotin doses (ie, >5 mg/day), no specimen should be taken until at least 8 hours after the last biotin administration.
For assays employing antibodies, the possibility exists for interference by human anti-animal antibodies (ie, heterophile antibodies) in the patient specimen. Patients who have been regularly exposed to animals or have received immunotherapy or diagnostic procedures utilizing immunoglobulins or immunoglobulin fragments may produce antibodies (eg human antimouse antibodies) that interfere with immunoassays. This may falsely elevate or falsely decrease the results. Interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin or ruthenium can occur.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.(1)
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
0-5 days: 0.7-15.2 mIU/L
6 days-2 months: 0.7-11.0 mIU/L
3-11 months: 0.7-8.4 mIU/L
1-5 years: 0.7-6.0 mIU/L
6-10 years: 0.6-4.8 mIU/L
11-19 years: 0.5-4.3 mIU/L
>20 years: 0.3-4.2 mIU/L
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Package insert: Roche TSH Reagent, Roche Diagnostics, Indianapolis, IN, 2010-08, V2
2. Fatourechi V, Lankarani M, Schryver P, et al: Factors influencing clinical decisions to initiate thyroxine therapy for patients with mildly increased serum thyrotropin (5.1-10.0 mIU/L). Mayo Clin Proc 2003 May;78(5):554-560
3. Wilson JD, Foster D, Kronenburg HM, et al: Williams Textbook of Endocrinology. Ninth edition. WB Saunders Company, 1998
4. Melmed S, Polonsky KS, Larsen PR, et al: Williams Textbook of Endocrinology. 12th edition. Elsevier Saunders Company, 2011, pp 348-414
5. Heil W, Ehrhardt V: Reference Intervals for Adults and Children 2008. Ninth edition. Roche Diagnostics Ltd, Rotkreuz, Switzerland July 2009, V9.1