TSH (THIRD GENERATION)

Order Code

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2835

Preferred Specimen

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Type: Serum

Volume: 2 mL

Collection Instructions:

Store refrigerated.

Collect in a Serum Separator Tube (SST).

Allow to clot upright for at least 30 minutes.

Centrifuge within 2 hours of collection.

ContainerType

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Serum separator tube

Alternate Specimen Requirements

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Plain Red Top Tube:

2 mL serum

Allow sample to clot upright for 60 minutes

Centrifuge and transfer serum to a plastic transport tube within 2 hours

Clearly label as: “Serum from plain red top tube”

Store refrigerated

Lithium Heparin Plasma (Green Top):

2 mL lithium heparin plasma

Centrifuge and separate plasma from cells immediately

Transfer plasma to a plastic transport tube

Clearly label as: “Lithium heparin plasma”

Store refrigerated

Note: Lithium heparin should only be used for primary testing

Minimum Volume

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0.75 mL serum
Pediatric volume: 0.25 mL serum (does not allow for repeat
or additional testing).

Transport Temperature

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Refrigerated

Expected Turnaround Time

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1 day

Specimen Stability

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8 days room temperature; 2 weeks refrigerated; 2 years frozen. Allow only one freeze/thaw cycle

Methodology

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Roche COBAS Electrochemiluminescent Immunoassay (ECLIA) this method has been standardized against the 2nd irp WHO reference standard 80/558.

Overview

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Thyroid Stimulating Hormone (TSH), or thyrotropin, is produced by the anterior pituitary and regulates thyroid hormone synthesis (T3, T4) through stimulation of the thyroid gland. It is regulated by thyrotropin-releasing hormone (TRH) from the hypothalamus and subject to negative feedback from circulating levels of T3 and T4.

The third-generation TSH assay used here detects down to ~0.005 mU/L and is the preferred screening test for thyroid dysfunction in stable patients.

Unlike T3/T4, TSH is not protein-bound, making it unaffected by changes in carrier protein levels due to pregnancy, steroids, liver/kidney disease.

Clinical Significance

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Screen for thyroid dysfunction

Diagnose hypo-/hyperthyroidism

Monitor thyroid replacement therapy

Guide TSH suppression therapy in thyroid cancer patients

Assess patients with:

• Goiter
• Palpitations
• Unexplained weight change
• Fatigue
• Depression

Newborn screening for congenital hypothyroidism

Additional Information

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Appropriate age to initiate TSH screening differs based on source. The American Thyroid Association advises every 5 years starting at age 35; the American Association of Clinical Endocrinologists advises screening women starting at age 50; and the U.S. Preventive Services Task Force (USPSTF) does not advise screening asymptomatic adults.

Patients on a steady replacement dose of T₄ should have levels checked annually.

Interpretative Information

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The third generation sensitive TSH (sTSH) can identify most cases of hypothyroidism and hyperthyroidism. In the setting of a healthy hypothalamic-pituitary-thyroid (HPT) axis, when peripheral T₄ levels are low, the intact feedback loop results in increased pituitary TSH production. When peripheral T₄ levels are high, pituitary TSH secretion is decreased. Exceptions to this generalization occur when there is damage to the hypothalamus or pituitary, alterations to normal HPT axis functioning due to medication (including recent changes in thyroxine therapy) (Guber, 2012), or nonthyroidal illness (euthyroid sick syndrome). Rarely a TSH-secreting tumor or thyroid hormone resistance can yield misleading results (Dayan, 2001).

In situations where the HPT axis is not functioning normally, or there is clinical concern of medication interference, TSH levels may be misleading and not consistent with clinical observations. In these cases, measuring the free T₄ and/or free T₃ levels may be helpful in clarifying the diagnosis.

Decreased TSH:

• Primary hyperthyroidism
• Subclinical hyperthyroidism
• Central hypothyroidism
• Acute nonthyroidal illness (ie, euthyroid sick syndrome)
• Drugs (eg, glucocorticoids, dopamine, amiodarone, bromocriptine)
• Over-the-counter supplements (eg, tyrosine, kelp, iodine)
• Surreptitious ingestion of thyroxine

Increased TSH:

• Primary hypothyroidism
• Subclinical hypothyroidism
• TSH-related conditions (eg, pituitary tumor or thyroid hormone resistance)
• Malabsorption of prescribed thyroxine (eg, small intestinal disease, cholestyramine)
• Drugs (eg, amiodarone, iodine, lithium, methimazole, propylthiouracil, radioiodine contrast)

False-normal TSH:

Central hypothyroidism due to pituitary or hypothalamic dysfunction

Early thyrotoxicosis

Subacute thyroiditis

Limitations

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• TSH is accurate only in steady-state conditions, which are present 4-6 weeks after starting or adjusting levothyroxine dose.
• Important to remember that it takes several weeks for TSH level to accurately reflect the current thyroxine concentrations following thyroid replacement therapy, thyroid ablation, or antithyroid medication for hyperthyroidism.
• High circulating levels of biotin can interfere with thyroid function assays, most commonly causing falsely high levels of T3, free T3 and free T4 and falsely low levels of TSH, leading to an incorrect diagnosis of hyperthyroidism or conclusion that thyroid hormone dose is too high. Results inconsistent with clinical picture should be investigated (Li 2017).

References

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Diagnostic Role

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• Hypothyroidism represents a deficiency in thyroxine (T₄) output relative to physiologic requirements.
• Primary hypothyroidism: Failure of the thyroid itself to secrete thyroid hormone resulting in low T₄ and T₃ levels, with the subsequent increase in TSH release by the pituitary. The most common cause is treatment for hyperthyroidism by radioactive iodine ablation or surgery. TSH elevation precedes a measured decreased in T₄ (total or free).
• Central hypothyroidism: Pituitary or hypothalamic dysfunction resulting in decreased TSH secretion (and TRH in the latter). TSH may be within or even slightly above reference range, but still too low relative to concurrently drawn low T₄ levels.
• Subclinical hypothyroidism: Elevated TSH with normal levels of T₄ and T₃; often due to thyroiditis or inadequate treatment of hypothyroidism. Presence of thyroperoxidase (TPO) antibodies increases risk of subsequent hypothyroidism, especially if free T₄ is marginally decreased.
• Hyperthyroidism represents an excess of thyroxine (T₄) output relative to physiologic requirements.
• Primary hyperthyroidism: Thyroid gland overproduction of thyroxine, resulting in down-regulation of TSH levels. TSH decrease precedes a measured increase in T₄ (total or free).
• Secondary hyperthyroidism: TSH levels increased due to TSH-secreting pituitary tumor (uncommon).
• Subclinical hyperthyroidism: Low TSH with normal levels of T₄ and T₃; typically due to excessive thyroid hormone replacement.
• Euthyroid sick syndrome: Severe nonthyroidal illness (eg, sepsis) may transiently affect thyroid hormones, binding proteins, and TSH concentrations resulting in abnormal laboratory values in a patient that does not have thyroid disease, a condition referred to as “euthyroid sick syndrome”. The TSH, T₃, and T₄ tend to decrease during acute illness, with return to normal or even elevated levels as the underlying condition resolves. Further complicating matters is that commonly used medications (eg, glucocorticoids, dopamine, opioids) affect TSH. Differentiation from inherent thyroid disease can be difficult biochemically. A clue to true thyroid disease would be findings of a goiter or thyroid nodule; a normal or elevated serum cortisol level favors euthyroid sick syndrome, whereas decreased serum cortisol and low gonadotropin levels favor central hypothyroidism (Umpierrez, 2002).
• Newborn screening for hypothyroidism: Congenital hypothyroidism occurs in approximately 1:4000 births and, if untreated, causes irreversible mental retardation, physical deformities, and even death. Screening with T₄ and/or TSH levels is advised within 2-4 days of birth, and is performed by various immunoassay methods on blood collected on special filter paper (AAP, 2006)

Alias

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• Third generation TSH
• Thyroid stimulating hormone (TSH)

Test Setup Days

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Monday through Friday PM shift

CPT

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84443 Limited Coverage Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Required
If Diagnosis Is Not Covered.
Frequency Limit Test For Medicare.
Advance Beneficiary Notice Of Non-Coverage (ABN) Always
Required For Frequency.
LOINC: 11579-0

CPT

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AGE 0-5 DAYS: 0.700-15.200 UIU/ML
6 DAYS-2 MONTHS: 0.700-11.000 UIU/ML
3-11 MONTHS: 0.700-8.400 UIU/ML
1-5 YEARS: 0.700-6.000 UIU/ML
6-10 YEARS: 0.600-4.800 UIU/ML
11-17 YEARS: 0.500-4.300 UIU/ML
>=18 YEARS: 0.400-4.100 UIU/ML