INTRODUCTION
Thyroid function tests (TFTs) is a collective term for test used to check the function of the thyroid gland.
Indications
Screening for Thyroid Dysfunction
Thyroid function tests are performed to screen patients suspected of having thyroid disease.
The indications for screening include:
•• Neonates for congenital hypothyroidism
•• Patients with autoimmune disease
•• Individuals with strong family history of thyroid diseases
•• Patient with suspected hyperthyroidism/hypothyroidism
•• Conditions linked to thyroid disease such as atrial fibrillation or anxiety disorder.
Surveillance
•• Women with a history of postpartum thyroiditis.
•• Post-neck irradiation.
•• Post-destructive treatment (radioiodine or surgical) for thyrotoxicosis.
Monitoring
One of the common reasons for assessing thyroid function is to monitor therapy.
•• Monitoring treatment of hyperthyroidism with anti-thyroid drugs.
•• Patients with primary hypothyroidism who are taking thyroxine hormone replacement therapy.
THYROID FUNCTION TESTS (BOX 65.1)
Serum Thyroid Hormones
Thyroid Stimulating Hormone/Thyrotrophin (TSH)
It is secreted by the anterior pituitary gland. It increases production and release of thyroxine (T3 and T4) form the thyroid. Its secretion is inhibited by high levels of T3 and T4.
It is stimulated by high levels of TRH and low levels of T3 and T4.
Use
To assess true metabolic status. It is the most important test to assess function and monitor thyroid hormone replacement therapy.
•• Increased: Thyroid failure is characterized by decrease in the level of T3 and T4 with increased TSH.
–– Primary hypothyroidism
–– Hashimoto thyroiditis.
•• Decreased: In hyperthyroidism TSH level is suppressed and may be undetectable.
Thyroid Hormone Levels
•• FT4 (Free thyroxine): It is produced only by the thyroid gland. It travels in plasma bound to protein or in free form. It is converted to T3 (active) and RT3 (inactive) peripherally in blood and tissues.
•• T3 (Triiodothyronine): T4 is converted to T3 in the peripheral tissue. Most of it is transported in plasma bound to protein and only 0.3% in free form.
Use
Its level reflects secretory activity.
•• Increased in hyperthyroidism
•• Decreased in hypothyroidism.
Thyrotrophin Releasing Hormone (TRH) Stimulation Test
TRH secreted by hypothalamus, which stimulates the release of TSH from the pituitary.
TRH secretion is inhibited by high levels of T3 and T4 and stimulated by low levels of T3 and T4. Serum TSH is measured before and after the intravenous administration of TRH.
Use (Box 65.2) To differentiate two forms (whether due to tumor or not) of thyrotrophin-induced hyperthyroidism.
•• In primary hypothyroidism an exaggerated prolonged rise of already increased TSH level is observed.
•• In secondary hyperthyroidism (pituitary), there will be no rise in the decreased TSH level.
Thyroglobulin (Tg)
It is secreted by thyroid follicular cells and is involved in iodination and synthesis of thyroid hormones.
Use
To predict the outcome of therapy for hyperthyroidism.
•• Increased
–– Well-differentiated thyroid carcinoma
–– Hyperthyroidism
•• Decreased: Total thyroidectomy or destruction of thyroid by radiation.
Calcitonin Level
It is secreted by the parafollicular C cells of the thyroid. It decreases the bone-resorption by osteoclasts and causes decreased serum calcium.
Use
Diagnosis of primary/recurrence of medullary carcinoma of thyroid or metastases after the removal of the primary.
•• Increased in:
–– Some paraneoplastic syndromes (e.g. carcinoma of lung)
–– Hypercalcemia of any cause
–– C cell hyperplasia.
Thyroid Autoantibody Tests
The different types of thyroid autoantibodies responsible for the autoimmune thyroid disorders are:
•• Anti-microsomal antibody.
•• Anti-thyroid peroxidase (TPO) antibody (TPOAb): They are involved in the tissue destructive process associated with hypothyroidism in Hashimoto and atrophic thyroiditis.
•• Anti-thyroglobulin (Tg) antibody.
•• TSH receptor (TR) antibody (TRAb): These antibodies were previously known as thyroid stimulating immunoglobulin (TSI) or long acting thyroid stimulators (LATS).
Laboratory assessment of anti-thyroid peroxidase antibodies is replacing the anti-microsomal and anti-thyroglobulin antibodies.
Uses of thyroid autoantibodies measurement is listed in Box 65.3.
Radioactive Iodine Uptake (RAIU)
T4 contains high iodine and the thyroid gland must take-up a large amount of iodine from the circulating blood for the synthesis of T4.
The iodine uptake activity of thyroid can be measured by administering orally a low dose of radioactive iodine (or technetium) and the radioactivity over the thyroid is measured at specified intervals. The amount of radioactivity that is taken up by the thyroid gland is known as radioactive iodine uptake (RAIU).
Normal uptake ranges from 10 to 35% in 24 hours. A very high RAIU is seen in hyperthyroidism, while a low RAIU is seen hypothyroidism.
Use
–– Evaluation of hyperthyroidism
–– Differentiate Graves from toxic goiter
–– Function of a thyroid nodule as hot or cold.
•• Increased: Graves disease, toxic multinodular goiter and adenoma and early thyroiditis.
•• Decreased: Hypothyroidism, late thyroiditis.
Contraindication: RAIU is contraindicated in children and during pregnancy/lactation.
Thyroid Scintiscanning
In addition to the radioactive iodine uptake, an isotype (99mTc-pertechnetate) can be administered and its distribution within the thyroid gland is assessed by gamma counter.
Use
•• Differential diagnosis of high RAIU thyrotoxicosis
–– Uniform or diffuse increase in uptake in Graves’ disease
–– Multiple discrete areas of increased uptake in toxic multinodular goiter
–– Single area of increased uptake in adenoma.
•• Evaluation of solitary nodule of thyroid
–– Hyper functioning: Hot nodule
–– Non-functioning: Cold nodule (~20% are malignant).
Common thyroid function tests in normal and pathological conditions is shown in Table 65.1.
Normal reference range for common thyroid functions are presented in Table 65.2.
Points to note:
•• Thyroid function tests are useful for evaluation of hyper or hypothyroidism. It is also useful for diagnosis of autoimmune diseases of thyroid.
•• Estimation of serum calcitonin is of value in diagnosis of primary or recurrence in medullary carcinoma.