THYROID FUNCTION TESTS

B Nagaraju

Pharm.D

Thyroid gland is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage The thyroid gland controls how quickly the body uses energy, makes proteins, and controls how sensitive the body is to other hormones.

It participates in these processes by producing thyroid hormones, the principal ones being Tri-iodothyronine (T3) and Thyroxine which can sometimes be referred to as tetraiodothyronine (T4).

These hormones regulate the rate of metabolism and affect the growth and rate of function of many other systems in the body.

T3 and T4 are synthesized from both Iodine and tyrosine. The thyroid also produces calcitonin, which plays a role in calcium homeostasis.

Hormonal output from the thyroid is regulated by thyroid stimulating Hormone (TSH) produced by the anterior pituitary, which itself is regulated by thyrotropin-releasing hormone (TRH) produced by the hypothalamus.

T4 has a longer plasma half- life than T3. However at cellular level T3 is more active physiologically.

The thyroid gets its name from the Greek word for "shield", due to the shape of the related thyroid cartilage.

The most common problems of the thyroid gland consist of an overactive thyroid gland, referred to as hyperthyroidism, and an underactive thyroid gland, referred to as hypothyroidism.

Anatomy

The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes.

The organ is situated on the anterior side of the neck, lying against and around the larynx and trachea, reaching posteriorly the oesophagus and carotid sheath.

Thyroid Disorders 

Patients with a normally functioning thyroid gland are said to be in a euthyroid state.

When this state is disrupted, thyroid disease may result. It occurs four times more often in women than in men and may occur at any age, but it peaks between the third and sixth decades of life.

A family history of this disease often is present, especially for the autoimmune thyroid diseases.

Diseases of the thyroid usually involve an alteration in the quantity or quality of thyroid hormone secretion and may manifest as hyperthyroidism or hypothyroidism.Enlargement of Thyroid gland is called as Goiter.

Hypothyroidism

Hypothyroidism results from a deficiency of thyroid hormone secretion, causing a generalized slowing of the metabolism.

Sysmtoms include lethargy, constipation, dry coarse skin and hair, paresthesias, cold intolerance, decreased sweating, impaired memory, confusion and dementia, slow speech and motor activity and anemia.

Hypothyroidism is usually caused by one of the three mechanisms:

1) Primary Hypothyroidism is failure of the thyroid to secrete thyroid hormone

2) Secondary Hypothyroidism is failure of the anterior pituitary to secrete TSH

3) Tertiary Hypothyroidism is failure of the Hypothalamus to secrete TRH

Hyperthyroidism

Thyrotoxicosis results when excessive amounts of thyroid hormones are circulating and usually is due to hyperactivity of the thyroid gland (Hyperthyroidism)

Its signs and symptoms include nervousness, fatigue, weight loss, Heat intolerance , increased sweating, tachycardia, moist skin and exophthalamos.

Thyroid Function tests:

Tests more specific for thyroid status or function can be categorized as follow:

1. Measure the concentration of products secreted by the thyroid gland.

2. Evaluate the integrity of the hypothalamic – pituitary – thyroid axis.

3. Assess inherent thyroid gland function.4. Detect antibodies to thyroid tissues.

Tests that directly or indirectly measure the concentration of T4 and T3 includes –

• Free T4• Total serum T4 • Serum T3 resin uptake• Free T4 Index• Total Serum T3 The integrity of hypothalamic pituitary thyroid axis is assessed by measuring –• TSH• TRH 

 Free Thyroxine:

Normal Range: 0.8 – 2.7 ng/dl or 10 – 35 pmol/L This test measure the unbound T4 in the serum and is the most accurate reflection of thyroid metabolic status.The low concentration of T4 in the serum ( Less than 1% of total T4), makes accurate measurement difficult and is a laborious process. Therefore, free T4 is assayed primarily when T4 binding globulin alteration or Non-thyroidal illness confirmed interpretation of Conventional tests.

 Total Serum Thyroxine

Normal range: 4 – 12 µg/dL or 51 – 154 nmol/L

Although ultrasensitive TSH and free T4 assays are gradually supplanting this RIA (radioimmunoassay), total serum T4 still is the standard initial screening test to assess thyroid function because of its wide availability and quick turnaround time.

In most patients, the total serum T4 level is a sensitive test for the functional status of the thyroid gland. It is high in 90% of hyperthyroid patients and low in 85% of hypothyroid patients.

Conditions that increase or decrease thyroid-binding protein result in an increased or decreased total serum Thyroid respectively, but do not affect the amount of metabolically active free T4 in the circulation.

 Increased Total serum Thyroxine

An increased total serum T4 may indicate Hyperthyroidism, elevated concentrations of thyroid-binding proteins or non-thyroid illness.

The transient elevations might be due to TSH secretion stimulated by a low T3 concentration. Similarly, up to 20% of all patients admitted to psychiatric hospitals have had transient total serum T4 elevation on admission. 

 Decreased Total serum Thyroxine

A decreased total serum T4 may indicate hypothyroidism, decreased concentrations of thyroid – binding proteins or non-thyroid illness (also called “euthyroid sick syndrome”).Non-thyroid illness may lower the total serum T4 concentration with change in thyrometabolic status.Typically in this syndrome, total serum T4 is decreased, total serum T3 is decreased and TSH is Normal.Neoplastic disease, DM, Burns, Trauma, liver disease, renal failure, prolonged infections and cardiovascular disease are non-thyroid illness that can lower Total serum T4 concentrations.

Mechanism Increase Total Serum T3 and Free T4

Decrease Total Serum T4 and Free T4

Interference in central regulation of TSH

secretion at hypothalamic – Pituitary level

Amphetamines Glucocorticoids

Interference with thyroid hormone synthesis and/or release from

thyroid

AmiodaroneIodides

AminoglutethimideAmiodarone

IodidesLithium Carbonate

Altered thyroid hormone metabolism

AmiodaroneIopanoic Acid

IpodatePropranolol (High Dose)

Phenobarbital

Inhibition of gastrointestinal

absorption of exogenous thyroid hormone

AntacidsCholestyramine

ColestipolIron

Soya bean flour

Drugs causing true alterations in total serum thyroxine

Serum Tri-iodothyroxine Resin Uptake

Normal range: 25-35 %

The T3 resin uptake test indirectly estimates the number of binding sites on thyroid – binding protein occupied by T3. This result is also referred to as thyroid hormone binding ratio.

The T3 resin uptake usually is high when the thyroid – binding protein is low and vice versa.Elevated T3 resin uptake concentrations are consistent with hyperthyroidism, while decreased concentrations are consistent with hypothyroidism. 

The T3 resin uptake is low in hypothyroidism because of the increased availability of binding sites on the thyroid-binding globulin. However, in non-thyroidal illness with a low T4, the T3 resin uptake is elevated. Therefore, the test may be used to differentiate between true hypothyroidism and a low T4 state caused by non-thyroid illness.

Free thyroxine Index

Normal range: 1.2 – 4.2

The free T4 index is the product of total serum T4 multiplied by the percentage of T3 resin uptake :

Free T4 index = total serum T4 (mg/dl) × T3 resin uptake (%)The free T4 index adjusts for the effects of alterations in thyroid – binding protein on the total serum T4 assay.The index is high in hyperthyroidism and low in hypothyroidism.

Patients taking phenytoin or salicylates have low total serum T4 and high T3 resin uptake with a normal free T4 index.Pregnant patients have high total serum T4 and low T3 resin uptake with a normal free T4 index.

 Total serum Tri-iodothyronine

Normal range : 78 – 195 ng/dL

As with the total serum T4 test, changes in thyroid – bindings protein increase or decrease total serum T3 but do not affect the metabolically active free T3 in the circulation. Therefore, the patients thyro-metabolic status remains unchanged.

The total serum T3 primarily is used as an indicator of hyperthyroidism. This Measurement usually is made to detect T3 toxicosis when T3 but not T4 is elevated.

Generally, the serum T3 assay is not a reliable indicator of hypothyroidism because of the lack of reliability in the low to normal range.

Thyroid Stimulating Hormone

Normal Range: 0.3 – 5 µU/mL

TSH assays have been useful in diagnosing primary hypothyroidism, they have not been useful in diagnosing hyperthyroidism.

Almost all patients with symptomatic primary hypothyroidism have TSH concentrations greater than 20 mU/L

Those with mild signs or symptoms have TSH values of 10 – 20 mU/L TSH concentrations often become elevated before T4 Concentarations decline.

The first generation TSH assay however can not distinguish low normal from abnormaly Low Values because their lower value of detection is 0.5 mU/L while the lower limit of basal TSH is 0.2 – 0.3 mU/L in most euthyroid persons.

Thyrotropin Releasing Hormone (TRH)

TRH is a hormone secreted by Hypothalamus, regulates TSH secretion from the pituitary .The TRH test measures the ability of injected TRH to stimulate the Pituitary to release TSH.

This test is the most indicator of Hyperthyroidism in patients whose other thyroid function are equivocal primarily with the older.

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