Laboratory assessment of thyroid function
- Douglas S Ross, MD
Douglas S Ross, MD
- Section Editor — Thyroid Disease
- Professor of Medicine
- Harvard Medical School
Secretion of the thyroid hormones T4 (thyroxine) and T3 (triiodothyronine) is regulated by pituitary thyroid-stimulating hormone (TSH) (figure 1 and figure 2). TSH secretion, in turn, is controlled through negative feedback by thyroid hormones (see "Thyroid hormone synthesis and physiology"). There is a negative log-linear relationship between serum free T4 and TSH concentrations . This means that very small changes in serum free T4 concentrations induce very large reciprocal changes in serum TSH concentrations. As a result, thyroid function is best assessed by measuring serum TSH, assuming steady-state conditions and the absence of pituitary or hypothalamic disease. Nevertheless, direct measurement of serum thyroid hormone levels is still important in many patients since it may be difficult in some patients to be certain about the state of pituitary and hypothalamic function.
This topic review will provide an overview of thyroid function testing. More detailed discussions of serum TSH and free thyroid hormone measurements, abnormalities in thyroid hormone binding proteins, and the effects of drugs and nonthyroidal illness on thyroid function tests are discussed separately. (See "Drug interactions with thyroid hormones" and "Thyroid function in nonthyroidal illness" and "Diagnosis of and screening for hypothyroidism in nonpregnant adults" and "Diagnosis of hyperthyroidism".)
LABORATORY TESTS USED TO ASSESS THYROID FUNCTION
Thyroid function is assessed by one or more of the following tests (table 1):
●Serum TSH concentration
●Serum total T4 concentration
- Spencer CA, LoPresti JS, Patel A, et al. Applications of a new chemiluminometric thyrotropin assay to subnormal measurement. J Clin Endocrinol Metab 1990; 70:453.
- Caldwell G, Kellett HA, Gow SM, et al. A new strategy for thyroid function testing. Lancet 1985; 1:1117.
- Nicoloff JT, Spencer CA. Clinical review 12: The use and misuse of the sensitive thyrotropin assays. J Clin Endocrinol Metab 1990; 71:553.
- Ross DS, Ardisson LJ, Meskell MJ. Measurement of thyrotropin in clinical and subclinical hyperthyroidism using a new chemiluminescent assay. J Clin Endocrinol Metab 1989; 69:684.
- Spencer CA, Takeuchi M, Kazarosyan M. Current status and performance goals for serum thyrotropin (TSH) assays. Clin Chem 1996; 42:140.
- Baloch Z, Carayon P, Conte-Devolx B, et al. Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease. Thyroid 2003; 13:3.
- Kratzsch J, Fiedler GM, Leichtle A, et al. New reference intervals for thyrotropin and thyroid hormones based on National Academy of Clinical Biochemistry criteria and regular ultrasonography of the thyroid. Clin Chem 2005; 51:1480.
- Surks MI, Hollowell JG. Age-specific distribution of serum thyrotropin and antithyroid antibodies in the US population: implications for the prevalence of subclinical hypothyroidism. J Clin Endocrinol Metab 2007; 92:4575.
- Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab 2012; 97:1554.
- Waring AC, Arnold AM, Newman AB, et al. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab 2012; 97:3944.
- Vadiveloo T, Donnan PT, Murphy MJ, Leese GP. Age- and gender-specific TSH reference intervals in people with no obvious thyroid disease in Tayside, Scotland: the Thyroid Epidemiology, Audit, and Research Study (TEARS). J Clin Endocrinol Metab 2013; 98:1147.
- Ekins R. The free hormone hypothesis and measurement of free hormones. Clin Chem 1992; 38:1289.
- Midgley JE. Direct and indirect free thyroxine assay methods: theory and practice. Clin Chem 2001; 47:1353.
- Wong TK, Pekary AE, Hoo GS, et al. Comparison of methods for measuring free thyroxin in nonthyroidal illness. Clin Chem 1992; 38:720.
- Larsen PR, Alexander NM, Chopra IJ, et al. Revised nomenclature for tests of thyroid hormones and thyroid-related proteins in serum. J Clin Endocrinol Metab 1987; 64:1089.
- Barbesino G. Misdiagnosis of Graves' Disease with Apparent Severe Hyperthyroidism in a Patient Taking Biotin Megadoses. Thyroid 2016; 26:860.
- Sharma A, Baumann NA, Shah P. Biotin-Induced Biochemical Graves Disease: A Teachable Moment. JAMA Intern Med 2017; 177:571.
- de los Santos ET, Starich GH, Mazzaferri EL. Sensitivity, specificity, and cost-effectiveness of the sensitive thyrotropin assay in the diagnosis of thyroid disease in ambulatory patients. Arch Intern Med 1989; 149:526.
- Surks MI, Chopra IJ, Mariash CN, et al. American Thyroid Association guidelines for use of laboratory tests in thyroid disorders. JAMA 1990; 263:1529.
- DeGroot LJ, Mayor G. Admission screening by thyroid function tests in an acute general care teaching hospital. Am J Med 1992; 93:558.
- Ross DS. Screening thyroid function tests in an acute-care hospital. Am J Med 1994; 96:393.
- Franklyn JA, Black EG, Betteridge J, Sheppard MC. Comparison of second and third generation methods for measurement of serum thyrotropin in patients with overt hyperthyroidism, patients receiving thyroxine therapy, and those with nonthyroidal illness. J Clin Endocrinol Metab 1994; 78:1368.
- Spencer C, Eigen A, Shen D, et al. Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients. Clin Chem 1987; 33:1391.
- Carr D, McLeod DT, Parry G, Thornes HM. Fine adjustment of thyroxine replacement dosage: comparison of the thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment. Clin Endocrinol (Oxf) 1988; 28:325.
- Ross DS, Daniels GH, Gouveia D. The use and limitations of a chemiluminescent thyrotropin assay as a single thyroid function test in an out-patient endocrine clinic. J Clin Endocrinol Metab 1990; 71:764.
- Ehrmann DA, Sarne DH. Serum thyrotropin and the assessment of thyroid status. Ann Intern Med 1989; 110:179.
- Barbesino G, Tomer Y. Clinical review: Clinical utility of TSH receptor antibodies. J Clin Endocrinol Metab 2013; 98:2247.
- LABORATORY TESTS USED TO ASSESS THYROID FUNCTION
- Serum TSH concentration
- Serum T4 and T3
- Serum free T4 and free T3
- T3-resin uptake
- Assay interference with biotin ingestion
- CLINICAL USE OF THYROID FUNCTION TESTS
- Screening for thyroid dysfunction
- Monitoring levothyroxine therapy
- Monitoring treatment of hyperthyroidism
- ANTITHYROID ANTIBODIES
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS