Thyroid Function Test

1. Thyroid-Stimulating Hormone (TSH)

What is TSH?

TSH is a hormone produced by the anterior pituitary gland. It stimulates the thyroid gland to synthesize and release thyroid hormones.

Why is TSH important?

TSH is usually the most sensitive initial laboratory test for detecting primary thyroid dysfunction.

Basic Interpretation

• High TSH → suggests reduced thyroid hormone production in primary hypothyroidism.
• Low TSH → suggests excess thyroid hormone production in primary hyperthyroidism.

Interpretation

However, TSH alone cannot correctly classify every thyroid disorder, particularly pituitary or hypothalamic disease.

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2. Free T4 (FT4)

T4 (thyroxine) is the major hormone released by the thyroid gland.

Most T4 circulates attached to proteins, while only a small amount remains free.

Importance of FT4

FT4 represents the hormone available to tissues and helps determine the severity and type of thyroid dysfunction.

Typical Patterns

• High TSH + Low FT4 → Primary hypothyroidism
• Low TSH + High FT4 → Primary hyperthyroidism
• High TSH + Normal FT4 → Subclinical hypothyroidism
• Low TSH + Normal FT4 → Subclinical hyperthyroidism

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3. Free T3 (FT3)

T3 is the more biologically active thyroid hormone.

A large proportion of T3 is produced by conversion of T4 in peripheral tissues rather than directly secreted by the thyroid.

Clinical Importance

FT3 is particularly useful when:

• Hyperthyroidism is suspected.
• TSH is low but FT4 is normal.
• T3 toxicosis is suspected.

T3 measurement is generally less useful for diagnosing hypothyroidism because T3 may remain normal even when thyroid hormone production is reduced.

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4. Total T4

Total T4 measures:

Free T4 + Protein-bound T4

Most circulating T4 is bound to proteins, particularly thyroxine-binding globulin (TBG).

Therefore, total T4 can change when binding-protein levels change, even when thyroid function is normal.

Factors Affecting Total T4

Changes may occur with:

• Pregnancy
• Estrogen therapy
• Changes in thyroid-binding proteins
• Certain medications

Therefore, FT4 is often preferred when available.

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5. Total T3

Total T3 measures both free and protein-bound T3.

It may be useful in selected patients with suspected hyperthyroidism, particularly when TSH is suppressed and FT4 is not elevated.

Like total T4, total T3 can be affected by changes in binding proteins.

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6. Anti-TPO Antibody

Anti-thyroid peroxidase (anti-TPO) antibody is an important marker of autoimmune thyroid disease.

Clinical Importance

It is commonly associated with:

• Hashimoto thyroiditis
• Autoimmune hypothyroidism
• Some patients with Graves disease

A positive anti-TPO result supports an autoimmune cause but should be interpreted with the clinical and biochemical findings.

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7. Thyroglobulin Antibody (TgAb)

Thyroglobulin antibodies are antibodies directed against thyroglobulin, a protein involved in thyroid hormone synthesis.

They may be present in:

• Hashimoto thyroiditis
• Other autoimmune thyroid disorders

TgAb testing is used in selected clinical situations rather than as a routine thyroid function test for every patient.

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8. TSH Receptor Antibody (TRAb)

TRAb targets the TSH receptor on thyroid cells.

Clinical Importance

TRAb is particularly useful for supporting the diagnosis of Graves disease, an autoimmune cause of hyperthyroidism.

It may also have importance in selected pregnancy-related situations because these antibodies can cross the placenta.

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Typical Laboratory Patterns

Important

Central hypothyroidism occurs because of pituitary or hypothalamic disease. In this condition, TSH may not be appropriately elevated despite a low FT4. Therefore, TSH should not be interpreted alone in suspected central disease.

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Specimen Required

• Specimen: Usually venous blood
• Sample: Serum or appropriate plasma, depending on the laboratory method
• The sample should be collected and handled according to the laboratory’s standard procedure.

Important Pre-Analytical Considerations

Thyroid test results can be influenced by:

• Pregnancy
• Severe non-thyroidal illness
• Certain medications
• Thyroid hormone treatment
• Biotin-containing supplements, which can interfere with some immunoassays

Therefore, relevant clinical history and medication/supplement use should be considered when interpreting unexpected results.

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Methods Used for Thyroid Testing

Modern laboratories commonly use automated immunoassays.

Depending on the laboratory analyzer, methods may include:

• Chemiluminescent immunoassay (CLIA)
• Electrochemiluminescence immunoassay (ECLIA)
• Other automated immunoassay techniques

The exact reference range depends on the laboratory method, analyzer, age, and patient population.

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Reference Ranges

Reference intervals vary between laboratories. Typical adult values may be approximately:

*These are general examples, not universal ranges. Always use the reference interval provided by the reporting laboratory.

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Clinical Interpretation

A. Hypothyroidism

In primary hypothyroidism:

TSH ↑ + FT4 ↓

Common causes include:

• Hashimoto thyroiditis
• Iodine deficiency
• Thyroid surgery
• Radioiodine treatment
• Certain drugs

B. Hyperthyroidism

In primary hyperthyroidism:

TSH ↓ + FT4 and/or FT3 ↑

Common causes include:

• Graves disease
• Toxic multinodular goiter
• Toxic adenoma
• Thyroiditis in some phases

C. Subclinical Hypothyroidism

TSH ↑ + FT4 normal

The patient may have few or no obvious symptoms.

D. Subclinical Hyperthyroidism

TSH ↓ + FT4 and FT3 normal

Clinical assessment and follow-up may be required depending on the degree of TSH suppression and the patient’s condition.

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Role of Thyroid Function Tests in Different Situations

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Clinical Significance

Thyroid function testing is important for:

• Diagnosis of hypothyroidism
• Diagnosis of hyperthyroidism
• Detection of subclinical thyroid disease
• Evaluation of autoimmune thyroid disorders
• Monitoring thyroid hormone replacement
• Monitoring treatment of hyperthyroidism
• Assessment of suspected pituitary or hypothalamic disorders
• Evaluation of abnormal thyroid-related symptoms

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Limitations

TFT results should not be interpreted without considering the clinical situation because:

• Pregnancy can change thyroid hormone physiology.
• Severe illness can alter thyroid test results.
• Medications can affect thyroid hormone levels or test measurements.
• Binding-protein changes can affect total T3 and T4.
• Laboratory methods may produce different reference ranges.
• A single abnormal result may require repeat testing or additional investigation.