THYROXINE HORMONE

Thyroxine

also tetraiodothyronine (T4), main hormone secreted by the thyroid gland. The role of T4 as a hormone with direct biological activity has been questioned, and some consider t4 to be a prohormone. However, t4 is known to have some direct biological activity.

Thyroglobulin

is a glycoprotein with a molecular weight of about 660,000 daltons. Thyroglobulin serves as a performed matrix containing 115tyrosyl groups to which reactive iodine is attached to form residues of monoiodotyrosine (MIT), diiodotyrosine (DIT), triiodothyronine (T3) and thyroxine(T4). After their formation, coupling of MIT and DIT takes place to form intrathyroglobulin T3 and T4. The thyroglobulin is then released from the calls into the colloidal of the follicle where it remains stored. The storage function of thyroglobulin provides a constant pool of thyroid hormone.

The released T3 and T4 are resistant to intrathyroid deiodanation and are secreted as active hormones. The daily secretion of thyroid hormone includes about 90mg of T4. and on their release into the bloodstream, circulating free T3 and T4 hormones enter the body cells, where they become part of an intracellular pool of hormone and be able to exert their metabolic effects. And now binding of thyroid hormones to proteins in the blood is accomplished by three proteins.

The most important is the thyroxine-binding globulin (TBG), it is a glycoprotein synthesized in the liver. The second most important is thyroxine-binding prealbumin (TBPA) and the third transporting protein is albumin.

The role of each of these proteins in the transport of T3 and T4 depends on their relative affinities for each of the thyroid hormones and on their relative concentrations in the plasma. Almost of the circulating T4 (99.95%) is bound to these plasma proteins.

All the circulating T4 originates in the thyroid gland, which secretes 80 to 100mg of T4 per day.

FUNCTION AFFECTING THROID FUNCTION

The extrinsic direct mechanism is represented by the HPTA (hypothalamic-pituitary-thyroid axis). The extrinsic indirect mechanisms emcompass a host a collateral factors of neourogenic, metabolic, and pharmacological nature.

The intrinsic mechanisms are those taking place within the thyroid cells. They are concerned with the maintenance of adequate amounts of intrathyroid hormone.

“Wolff- Chaikoff effect” inhibition of the formation and release of thyroid hormone ,when the thyroid is exposed to rapid and large increases of iodine.
Drugs, such as amiodarone is an antiarrhythmic drug that causes inhibition of T4 monodeiodination. This results in elevatios of free and total T4, decreasedT3.

Specimen Collection and storage

The preferred specimen is serum; plasma with EDTA or heparin as anticoagulant may also be used.

Note:plasma tends to form fibrin clots after freezing and thawing. T4 in serum is quite stable; storage of serum at room temperature up to 7 days results in no appreciable loss of T4.

DETERMINATION OF THYROXINE IN SERUM

Immunoassay

is the method of choice for measuring T4 in the clinical laboratory. Binding of T4 to TBPA is overcome by the use of barbital buffers. Other blocking agents such as 8-anilo-1-naphthalene-sulfonic acid(ANS), salicylate, thimerosal (methiolate), and phenytoin can be used, immunoassays for T4 can be classified as either isotonic or nonisotopic.

Isotonic Methods

Radioactive iodine has been widely employed as marker in RIA methods to follow and measure the distribution of T4 between unbound and antibody-bound fractions. Commercial RIA kits differ in their approach to separation of free and bound labeled T4 fractions. Kit procedures require only 1-hour incubation either at room temperature or at 37 degree Celsius. Sample volumes per test are small (about 25ul)

Nonisotonic methods

A variety of sensitive labels are used in nonisotonic immunoassays for T4. For example, enzymes such as horseradish peroxidaes, alkaline phosphate and beta-L-galactosidase are widely used as labels, as are fluorescent and chemiluminescent molecules.

PATHOLOGICAL CONDITIONS:

>Hyperthyroidism

- refers to the clinical syndrome caused by an excess circulating active thyroid hormone.

A.Grave’s disease
is caused by an immunological disorder in which serum antibodies bind to TSH receptors in the thyroid cell and stimulate the production and release of thyroid hormone.

Grave’s disease is characterized clinically by the presence of diffuse goiter (enlarged thyroid gland), ophthalmopathy, and occasionally pretibial edema. Grave’s ophthalmopathy is characterized by myxedematous infiltration of the tissue and muscles of the orbit, resulting in protrusion of the eyes and ocular muscle dysfunction.

B. Thyroiditis

Is a general term used to described an inflammation of the thyroid gland. All forms of thyroiditis can potentially cause hyperthyroidism because large quantities of hormone can be released from the inflamed and disrupted follicle.

Hypothyroidism

Clinical state of hypothyroidism develops whenever insufficient amounts of thyroid hormone are available to tissues.

Hashimoto’s thyroiditis

chronic lymphocytic thyroiditis is occasionally associated with an overactive thyroid state but more often results in hypothyroidism. It is believed to result from a derangement of the cell-mediated and humoral compartments of the immune system.

Goiter

- refers to an enlargement of the thyroid gland.


References:

Chemistry for Medical Technoologies
by: White.Erickson.Stevens

Tietz
Fundamentals of Clinical chemistry.4th edition

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