Thyroid-Stimulating Hormone 

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Age-specific and pregnancy-specific reference intervals have been established. There are no significant sex or race specific differences.

Expected values using a third-generation immunochemiluminometric assay are as follows:

The concentration of TSH in circulation is expressed as milli-international units of biological activity per liter of serum (mIU/L). This way of expressing the concentration originates from the way in which the TSH (and other hormones) was initially evaluated. TSH was initially measured using bioassay on colloidal tissue isolated from the guinea pig thyroid gland and an international unit was defined as the minimum amount of TSH that would elicit a biological response (stimulation of thyroid cAMP cyclase activity in these preparations). Currently all TSH assays are using WHO purified calibrators (second IRP 80/558), which have 7-5 pg purified human pituitary extract and are the equivalent of 37 mIU. (It should be noted that the pituitary extracts also contain small amounts of luteinizing hormone (LH) and follicle-stimulating hormone (FSH): 5-5% LH and 2-77% FSH. ^[1]

Conditions associated with increases in TSH include the following:

Congenital hypothyroidism

Primary hypothyroidism

TSH-secreting pituitary tumors (uncommon)

Pituitary resistance to thyroid hormone (uncommon)

Typical Laboratory Results in the Progression of Hashimoto Thyroiditis from Subclinical to Overt Disease (Open Table in a new window)

Stage of Disease

TSH

fT4

T3

Subclinical

Increased

Normal concentrations

Normal concentrations

Early

Increased

Decreased

Normal concentrations

Mature

Increased

Decreased

Decreased

Conditions associated with decreases in TSH include the following:

Hyperthyroidism

Pituitary (secondary) hypothyroidism (rare)

Nonthyroid illness

Typical Laboratory Results in the Progression of Graves Disease from Subclinical to Overt Disease (Open Table in a new window)

Stage of Disease

TSH

fT4

T3

Subclinical

Decreased

Normal concentrations

Normal concentrations

Early

Decreased

Normal concentrations

Increased

Mature

Decreased

Increased

Increased

Hypothyroidism

Signs or symptoms of hypothyroidism include the following:

Hyperthyroidism

Signs or symptoms of hyperthyroidism include the following:

Other considerations

Drugs that can increase TSH include the following:

Drugs that can decrease TSH include the following:

Preferred specimen and acceptable tubes:

Serum (red top tube, SST)

Plasma (green top tube – sodium heparin, ammonium heparin, lithium heparin; PST)

Whole blood – newborn screening, collected by heel puncture 48-72 hours after birth

Specimen volume: 0.5 mL plasma or serum (0.25 mL minimum volume)

Specimen stability:

Centrifuge specimens and remove serum or plasma from the cells within 2 hours of collection.

Store at room temperature for 8 hours, or refrigerate at 2-8 degrees Celsius (36-46 degrees Fahrenheit) up to 5 days.

If assays are not completed within 48 hours, or the separated sample is to be stored beyond 48 hours, samples should be frozen at -20 degrees Celsius or colder. Frozen samples should be thawed only once. Analyte deterioration may occur in samples that are repeatedly frozen or thawed.

Related tests:

Thyroxine (T4)

Triiodothyronine (T3)

Antithyroid autoantibodies

Thyroxine binding proteins

Thyroglobulin (Tg)

Thyrotropin-releasing hormone (TRH)

Measurement of TSH

There are two major ways in which TSH is currently evaluated: Radioimmunoassay (RIA) and chemiluminescence immunoassays.

In the RIA, endogenous TSH present in the sample is competing with radiolabeled TSH for a limited amount of TSH-specific antibodies (“competitive assay”). The measured signal is inversely proportional with the amount of TSH present in the sample. ^[2]

The chemiluminescence assay is using two antibodies (“sandwich immunoassay”). The “capture antibody” is binding usually within the alpha subunit of TSH, while the “detection antibody” is always binding within the TSH-specific beta-subunit. The measured signal is directly proportional with the amount of TSH present in the sample. The chemiluminescence assay is significantly more sensitive than RIA; the current generation of immunometric assay (the fourth generation) has a functional detection limit of 0.001-0.002 mIU/L. ^[2]

As with all immunoassays, these assays are prone to specific interferences, especially heterophilic antibodies. Hook effect is rarely seen. Macro TSH can also be considered in the face of spurious results that do not match the clinical conditions and if other interferences are eliminated as well.

Thyroid-stimulating hormone (TSH) is produced by the adenohypophysis. It promotes development of the thyroid gland and maintenance of its normal function. TSH stimulates the thyroid to produce and release the thyroid hormones: T4 and T3 (hypothalamus-pituitary-thyroid axis). Measurement of TSH frequently is included with that of T4 and T3 in a laboratory panel to screen for and to evaluate thyroid disease. The diagnosis of thyroid disorders can be complex, requiring the combined results of thyroid testing. ^{[3, 4, 5, 6, 7, 2]}

Indications for TSH testing include the following:

Screening for congenital hypothyroidism in newborns ^{[2, 1]}

Screening for subclinical hypothyroidism ^[8]

Diagnosis and monitoring of other thyroid disorders

Monitoring of patients receiving thyroid hormone

Mitchell ML, Hsu HW, Sahai I. Changing perspectives in screening for congenital hypothyroidism and congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes. 2014 Feb. 21 (1):39-44. [Medline].

Leger J, Olivieri A, Donaldson M, et al. ESPE-PES-SLEP-JSPE-APEG-APPES-ISPAE, Congenital Hypothyroidism Consensus Conference Group. European Society for Paediatric Endocrinology consensus guidelines on screening, diagnosis, and management of congenital hypothyroidism. J Clin Endocrinol Metab. 2014 Feb. 99 (2):363-84. [Medline].

Lee SL. Hyperthyroidism. Medscape Drugs & Diseases. September 4, 2014. [Full Text].

Orlander PR. Hypothyroidism. Medscape Drugs & Diseases. April 21, 2014. [Full Text].

Burris CA, Ashwood ER, Burns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4th ed. St. Louis: Elsevier Saunders; 2006.

McPherson RA, Matthew R. Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 22nd ed. Philadelphia: Elsevier Saunders; 2011.

Wallach J. Interpretation of Diagnostic Tests. 6th ed. New York: Little, Brown; 1996.

Rugge JB, Bougatsos C, Chou R. Screening and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Jan 6. 162 (1):35-45. [Medline].

Gaines Das RE, Bristow AF. The Second International Reference Preparation of Thyroid-Stimulating Hormone, Human, for Immunoassay: calibration by bioassay and immunoassay in an international collaborative study. J Endocrinol. 1985 Mar. 104 (3):367-79. [Medline].

William Clarke, ed. Contemporary Practice in Clinical Chemistry. 2nd Ed. 2011.

Stage of Disease

TSH

fT4

T3

Subclinical

Increased

Normal concentrations

Normal concentrations

Early

Increased

Decreased

Normal concentrations

Mature

Increased

Decreased

Decreased

Stage of Disease

TSH

fT4

T3

Subclinical

Decreased

Normal concentrations

Normal concentrations

Early

Decreased

Normal concentrations

Increased

Mature

Decreased

Increased

Increased

Alina G Sofronescu, PhD, NRCC-CC, FACB Assistant Professor, Board Certified Clinical Chemist, Medical Director of Clinical Chemistry Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Center

Alina G Sofronescu, PhD, NRCC-CC, FACB is a member of the following medical societies: American Association for Clinical Chemistry, Canadian Society of Clinical Chemists

Disclosure: Nothing to disclose.

Thomas M Wheeler, MD Chairman, Department of Pathology and Immunology, WL Moody, Jr, Professor of Pathology, Professor of Urology, Baylor College of Medicine

Thomas M Wheeler, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American Medical Association, American Society for Clinical Pathology, American Society of Cytopathology, American Thyroid Association, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Harris County Medical Society

Disclosure: Received stock from PathXL for medical advisory board. for: PathXL, Inc.

Thyroid-Stimulating Hormone 

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