Thyroid Gland Functions

Thyroid is an endocrine gland situated at the root of the neck on either side of the trachea. It has two lobes, which are connected in the middle by an isthmu. It weighs about 20 to 40 g in adults. Thyroid is larger in females than in males. The structure and the function of the thyroid gland change in different stages of the sexual cycle in females. Its function increases slightly during pregnancy and lactation and decreases during menopause.

HISTOLOGY OF THYROID GLAND

Thyroid gland is composed of large number of closed follicles. These follicles are lined with cuboidal epithelial cells, which are called the follicular cells. Follicular cavity is filled with a colloidal substance known as thyroglobulin, which is secreted by the follicular cells. Follicular cells also secrete tetraiodothyronine (T4 or thyroxine) and tri-iodothyronine (T3). In between the follicles, the parafollicular cells are presen.

These cells secrete calcitonin.

HORMONES OF THYROID GLAND

Thyroid gland secretes three hormones:

1. Tetraiodothyronine or T4 (thyroxine)

2. Tri-iodothyronine or T3

3. Calcitonin.

T4 is otherwise known as thyroxine and it forms about 90% of the total secretion, whereas T3 is only 9%

to 10%.

Chemistry

Both T4 and T3 are iodine-containing derivatives of amino acid tyrosine.

Potency and Duration of Action

The potency of T3 is four times more than that of T4. T4 acts for longer period than T3. Duration of T4 action is four times more than T3 action. This is because of the difference in the affinity of these hormones to plasma proteins. T3 has less affinity for plasma proteins and combines loosely with them, so that it is released quickly. T4 has more affinity and strongly binds with plasma proteins, so that it is released slowly. Therefore, T3 acts on the target cells immediately and T4 acts slowly.

Half-life

Thyroid hormones have long half-life. T4 has a long halflife of 7 days. Half-life of T3 is varying between 10 and 24 hours.

Rate of Secretion

Thyroxine = 80 to 90 μg/day

Tri-iodothyronine = 4 to 5 μg/day

Reverse T3 = 1 to 2 μg/day.

Plasma Level

Total T3 = 0.12 μg/dL

Total T4 = 8 μg/dL.

Metabolism of Thyroid Hormones

Degradation of thyroid hormones occurs in muscles,

liver and kidney

SYNTHESIS OF THYROID HORMONES

Synthesis of thyroid hormones takes place in thyroglobulin, present in follicular cavity. Iodine and tyrosine are essential for the formation of thyroid hormones. Iodine is consumed through diet. It is converted into iodide and absorbed from GI tract. Tyrosine is also consumed through diet and is absorbed from the GI tract. For the synthesis of normal quantities of thyroid hormones, approximately 1 mg of iodine is required

per week or about 50 mg per year. To prevent iodine deficiency, common table salt is iodized with one part of sodium iodide to every 100,000 parts of sodium chloride.

STAGES OF SYNTHESIS OF THYROID HORMONES

Synthesis of thyroid hormones occurs in five stages:

1. Thyroglobulin synthesis

2. Iodide trapping

3. Oxidation of iodide

4. Transport of iodine into follicular cavity

5. Iodination of tyrosine

6. Coupling reactions.

1. Thyroglobulin Synthesis

Endoplasmic reticulum and Golgi apparatus in the follicular cells of thyroid gland synthesize and secrete

thyroglobulin continuously. Thyroglobulin molecule is a large glycoprotein containing 140 molecules of amino acid tyrosine. After synthesis, thyroglobulin is stored in the follicle.

2. Iodide Trapping

Iodide is actively transported from blood into follicular cell, against electrochemical gradient. This process is called iodide trapping. Iodide is transported into the follicular cell along with sodium by sodium-iodide symport pump, which is also called iodide pump. Normally, iodide is 30 times more concentrated in the thyroid gland than in the blood. However, during hyperactivity of the thyroid gland, the concentration of iodide increases 200 times more.

3. Oxidation of Iodide

Iodide must be oxidized to elementary iodine, because only iodine is capable of combining with tyrosine to form thyroid hormones. The oxidation of iodide into iodine occurs inside the follicular cells in the presence of thyroid peroxidase. Absence or inactivity of this enzyme stops the synthesis of thyroid hormones.

4. Transport of Iodine into Follicular Cavity

From the follicular cells, iodine is transported into the follicular cavity by an iodide-chloride pump called

pendrin.

5. Iodination of Tyrosine

Combination of iodine with tyrosine is known as iodination. It takes place in thyroglobulin. First, iodine is

transported from follicular cells into the follicular cavity, where it binds with thyroglobulin. This process is called organification of thyroglobulin. Then, iodine (I) combines with tyrosine, which is already present in thyroglobulin. Iodination process is accelerated by the enzyme iodinase, which is secreted by follicular cells. Iodination of tyrosine occurs in several stages.

Tyrosine is iodized first into monoiodotyrosine (MIT) and later into di-iodotyrosine (DIT). MIT and DIT are called the iodotyrosine residues.

6. Coupling Reactions

Iodotyrosine residues get coupled with one another. The coupling occurs in different configurations, to give rise to different thyroid hormones.

Coupling reactions are:

i. One molecule of DIT and one molecule of MIT combine to form tri-iodothyronine (T3)

ii. Sometimes one molecule of MIT and one molecule of DIT combine to produce another form of T3 called reverse T3 or rT3. Reverse T3 is only 1% of thyroid output

iii. Two molecules of DIT combine to form tetraiodothyronine (T4), which is thyroxine.

Tyrosine + I = Monoiodotyrosine (MIT)

MIT + I = Di-iodotyrosine (DIT)

DIT + MIT = Tri-iodothyronine (T3)

MIT + DIT = Reverse T3

DIT + DIT = Tetraiodothyronine or Thyroxine (T4)

STORAGE OF THYROID HORMONES

After synthesis, the thyroid hormones remain in the form of vesicles within thyroglobulin and are stored for

long period. Each thyroglobulin molecule contains 5 or 6 molecules of thyroxine. There is also an average of 1 tri-iodothyronine molecule for every 10 molecules of thyroxine.

In combination with thyroglobulin, the thyroid hormones can be stored for several months. Thyroid

gland is unique in this, as it is the only endocrine gland that can store its hormones for a long period of about 4 months. So, when the synthesis of thyroid hormone stops, the signs and symptoms of deficiency do not appear for about 4 months.