Thyroid endocrine physiology

2021-06-17 04:35 PM

Iodine capture requires energy, thanks to the iodine pump, with the action of Na K ATPase, this process can be stopped by ouabain.

Anatomical and organizational features

The thyroid gland is in front of the trachea, under the thyroid cartilage, weighs 20-25g, includes 2 lobes, has a waist in the middle, 6cm high, 3cm wide, 2cm thick.

The structure consists of many thyroid follicles, filled with colloidal fluid, interspersed with a very rich vascular system (1% of cardiac output), where T3, T4 hormones are synthesized and stored.

Picture: Thyroid cyst.

Thyroid cysts are composed of glandular cells, the base is in contact with the capillaries, and the top of the cells is in contact with the colloidal fluid in the lumen.

In addition, adjacent to the thyroid follicles, parafollicular cells secrete calcitonin, a hormone involved in calcium metabolism (Figure 4).

Thyroid hormone synthesis

Iodine is essential for the synthesis of thyroid hormone. The synthesis of hormones consists of four stages:

Catching Iodine

In the thyroid, iodine capture must be present by TSH. It increases when the gland is stimulated by TSH or when hormone reserves in the thyroid gland decrease.

Plasma iodine circulates in the blood as iodine (I-) from the following sources:

From food, on average 100 to 300 micrograms per day

From the peripheral deiodination of thyroid hormone

Finally, iodine is obtained from the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT).

 Iodine uptake by the thyroid gland is reduced if the supply exceeds 4 mg/day.

Iodine capture requires energy, thanks to (iodine pumping (with the action of Na-K-ATPase, this process can be blocked by ouabain and perchlorate, which compete with iodine. Once inside the cell.) In the thyroid gland, these iodides will mix with the iodur released after thyroid hormone secretion and quickly be used to synthesize new thyroid hormone molecules. In a normal thyroid, the iodine pump concentrates iodine in the thyroid gland 30 times more. In an overactive thyroid, this concentration can increase up to 250 times.

Synthesis and storage of thyroid hormone

Thyroglobulin-binding thyroid hormone synthesis and storage. This substance is necessary for ionization and creates a reserve form of thyroid hormone before it is excreted.

In thyroid cells, the endoplasmic reticulum and Golgi reticulum synthesize and secrete thyroglobulin into the colloid, which is a genetically encoded 660,000 molecular weight glycoproteins. A thyroglobulin molecule has 2 subunits with equivalent molecular weights (330,000), but in colloids, it is in a heterogeneous form.

Iodine oxidation: The first step in thyroid hormone formation is the oxidation of I-- to iodine (I2), which is the form that can bind to the amino acid tyrosine residue of the thyroglobulin molecule. This process involves the enzyme peroxidase and it is accompanied by hydrogen peroxidase. Peroxidase is localized to the apex of the thyroid cells, and iodine oxidation occurs at the site where thyroglobulin is formed and dumped into the colloid. When the peroxidase system is blocked or due to congenital deficiency, the rate of thyroid hormone formation drops to zero.

Iodine binding to tyrosine: The binding of iodine to the thyroglobulin molecule is called the organization of thyroglobulin and the 1/6th degree of tyrosine residue on the thyroglobulin molecule by the enzyme iodinate. First, tyrosin is attached to 1 and 2 iods to form MIT (T1) and DIT (T2). Then within minutes, hours or days, the DITs pair to form thyroxin, an MIT pair with a DIT to form Triiodothyronine T3.

Thus, T3T4 is formed, which is the thyroid hormone and remains attached to the thyroglobulin molecule as a reserve.

Each thyroglobulin molecule contains 1 to 3 T4 and 14 thyroxin has 1 T3 molecule. In this form, thyroid hormone stored in a colloidal fluid is enough to supply the body for 2-3 months.

The organic process is self-regulated by the amount of I-- present in the thyroid cells: in the gland that was previously strongly stimulated, or because of iodine deficiency, or due to exogenous TSH, or an excess of iodine, leading to increased concentrations. iodine levels in thyroid cells. This leads to two consequences: (i) formation of inactive iodine (I3) which interferes with thyroid hormone synthesis (ii) excess iodine which interferes with iodine uptake, which of course leads to a decrease in I- in the thyroid and decrease in thyroid hormone.

However, the impediment to hormone synthesis will clear up after a while. This self-regulation is known as the Wolff-Chaikoff effect.

Thyroid hormone movement

This process is the opposite of iodine uptake: from the colloidal fluid through the cell and from the apical to the vascular terminal. Begins with the formation of prostheses in the parietal membranous villi of the thyroid cells. They will take the colloidal droplets to create a pocket in its interior, and then combine with lysosomes containing digestive enzymes. Proteinase is one of these enzymes, digesting the thyroglobulin molecule and releasing T3, T4 by cutting the peptide bonds that bind the hormone to the protein molecule. Hormones diffuse to the vascular poles to empty into surrounding capillaries, some into the lymphatic ducts.

About three-quarters of the tyrosine that has been iodized in thyroglobulin remains in the form of MIT and DIT. Along with the release of T3, T4, these forms are also released, but not into the blood, but deiodinase by deiodinase. It is this iodine that returns to the gland to contribute to the creation of new thyroid hormones.

Thyroid hormone secretion

Approximately 93% of the hormone released from the thyroid gland is thyroxine (100 nmol/24 h) and just over 7% is T3 (10 nmol/24 h). After a few days, most of the T4 is deionized to form T3. Finally, the hormone that arrives and acts on the tissue is mainly T3, where about 35 micrograms of T3 are made per day but they are inactive and can be destroyed.

Total plasma T4 concentrations are in the range of 50-140 nmol/l and T3 is 1.2-3.4 nmol/l, most of which are bound to plasma proteins. Free T3, Free T4 is measured directly by radioimmunoassay, free T4 (f-T4) is 12 pmol/l, free T3 (f-T3) is 30 pmol/l, this is the active form. of hormones.

Thyroid hormone metabolism

In the blood, most of T4 is converted into T3 and RT3 (reverse T3), T3 is a hormone that acts on tissues (80% converted to T4, 20% directly secreted by the thyroid gland), with 5 times more biological activity than T4. .

After acting, thyroid hormone is deionized in the liver, kidneys and many other tissues, some iodine will be reabsorbed into the blood to be used again, some excreted in the faeces.

Rates of reabsorption and excretion depend on the source of iodine. For example every day the body gets 500 (g of iodine from food and water), about 120 (g into the thyroid gland and the thyroid gland will use 80 (g to make T3, T4, and 40 (g) diffuse into the body). After that, T3, T4 are deionized, releasing 60(g. In total, there are about 600(g of iodine in the body every day), 20( will be reabsorbed into thyroid gland, 80( will be eliminated by Urine quantification of iodine in urine to know the amount of iodine in daily income.

Thyroid hormone effects

Effects on cell metabolism

T4, T3 increases O2 consumption in almost all tissues in the body, so it increases basal metabolism (CHCS), except brain, testes, uterus, spleen, lymph, and pre-yen. CHCS can increase from 60 to 100% above normal when large amounts of hormone are secreted.

Increase the size and number of mitochondria, thereby increasing ATP to provide energy for the body's functional activities.

When T3, T4 is too high (hyperthyroidism), the mitochondria increase activity, energy does not accumulate in the form of ATP but is released as heat.

Thyroid hormone has the effect of activating the enzyme Na + -K + -ATPase, thereby increasing the transport of Na + and K + ions across the cell membranes of some tissues, this process requires energy and increases thermogenesis. increase body metabolism.

Effects on growth

It is evident in the growing period of the child, along with GH to make the body develop. Especially effective in foetal brain development and the first years after birth.

Effects on metabolism 

Glucid: Thyroid hormone affects almost all stages of glucose metabolism, including increased glucose uptake in the intestine, increasing new sugar production, increasing the breakdown of glycogen into glucose in the liver, thereby causing hyperglycaemia but only increasing light.

Lipids: increased lipid degradation in adipose tissue, causing increased plasma free fatty acid concentrations and increased tissue oxidation of free fatty acids for energy. Reducing the amount of cholesterol, phospholipids, and triglycerides in the blood plasma, so people with hypothyroidism can have atherosclerosis.

Protide: At physiological doses, T3, T4 increase protein synthesis to help body development and growth, but at high doses, the catabolic effect is prominent, causing protein loss in tissues, so patients with hyperthyroidism is usually skinny.

Effects on vitamin metabolism 

T3, T4 are needed for the absorption of vitamin B12 in the intestine and the conversion of carotene to vitamin A.

Effects on the neuromuscular system

Thyroid hormone promotes intellectual development, high doses cause vivacity, restlessness, excitement; Children with disabilities cause mental retardation.

Synaptic activation shortens the time of synaptic conduction, so in patients with hyperthyroidism, the time of tendon reflexes is short, and at the same time, increases the activity of nerve synapses in the medulla area that govern muscle tone, causing signs and symptoms. muscle tremors.

Effects on the heart

On the heart increases the number (-receptors in the heart, so the heart is more sensitive to catecholamines, causing tachycardia.

On blood vessels: increased metabolism and increased metabolic products in tissues cause vasodilation, increasing cardiac output, sometimes increasing by more than 60% in hyperthyroidism and decreasing to only 50% of normal in hypothyroidism.

Effects on the genitals

The normal functioning of the thyroid gland is necessary for the normal development of the gonads. In men, lack of thyroid hormone causes loss of sex drive, but excessive secretion can cause impotence. In women, thyroid hormone deficiency causes menorrhagia and polymenorrhagia, but excess hormone causes amenorrhea, amenorrhea, or hypogonadism.

Regulate thyroid hormone secretion

The thyroid is controlled by pre-pituitary TSH, TSH secretion increases under the effect of TRH and cold decreases under stress, heat... Free T4, T3 reverses TSH secretion, TSH is controlled by TSH. TRH.

Under physiological conditions, only 55 (g iodine/day) is required to enter the thyroid gland, if the supply is increased (10 drops of Lugol contains 60,000 (g iodine) there appears to be a decrease in organic iodine uptake, as well as inhibition of release. hormones.

Thyroid dysfunctions

Thyroid superiority

The most common form of hyperthyroidism is Graves' disease (Basedow) with enlarged and protruding eyes. This is an autoimmune disease, the body produces antibodies against thyroid antigens, the antibodies bind to the TSH receptor to stimulate the secretion of thyroid hormone, this antibody is called TSI (Thyroid Stimulating Immunoglobulin). Radioimmunoassay have shown a decrease in TSH, sometimes as low as 0. In most patients, anti-foveal tissue antibodies are detected in the blood.

In addition, hyperthyroidism is also seen in thyroid tumours, more rarely, high levels of thyroid hormone inhibit the secretion of TSH by the pituitary gland so that the rest of the thyroid is almost inactive. All clinical symptoms of hyperthyroidism are caused by increased blood levels of T3, T4.

Weakness of the thyroid gland

The cause is thyroid, pituitary or hypothalamus, most commonly autoimmune hypothyroidism. Usually manifested by thyroiditis, then the thyroid gland gradually fibrosis and decreased function.

Hypothyroidism syndrome due to hypothyroidism, decreased thyroxine levels, patients are often sluggish, slow heart rate, sleep a lot... Manifestations of myxoedema are oedema caused by subcutaneous stasis of hyaluronic acid and chondroitin sulphate with protein. in the interstitial space. In addition, people with hypothyroidism may have atherosclerosis due to increased blood cholesterol levels, especially in hypothyroidism with myxoedema.

Dwarf thyroid (cretinism: Cretinisme): children with hypothyroidism soon after birth, short, intellectually underdeveloped, large tongue. Caused by maternal iodine deficiency during pregnancy or congenital thyroid abnormalities. Can be treated immediately after birth.

Iodine deficiency: when the absorption of iodine is less than 10 (g/day, the synthesis of thyroid hormone is insufficient, the TSH increases, causing hypertrophy of the thyroid gland: Local goitre In the early stages, thyroid function is normal, but if not controlled, Treatment will gradually lead to hypothyroidism.

The policy of providing iodized salt has been implemented in many countries and the results have significantly reduced the goitre rate. In our country, through surveys in the plains and even the coastal areas, there is iodine deficiency. From January 1995, the whole population was provided with iodized salt.

In addition, there are some other causes that prevent the synthesis of thyroid hormone (cassava, vegetables, tobacco...) causing scattered goitre.

Excess iodine

When iodine supply exceeds the prescribed limit (> 400-1000 (g / day) for a long time, it can cause thyroid dysfunction.

calcitonin hormone

Due to secretion by parafollicular cells, it accounts for only 0.1% of the thyroid gland. This is a polypeptide with 32 amino acids, molecular weight 3400.

The effect of reducing plasma calcium concentration by reducing the activity of osteoclasts, increasing the deposition of calcium salts in the bone, and reducing the formation of new osteoclasts. The above effect is important in the growing child in response to the rapid rate of bone change during the growing period.

The excretion of calcitonin is regulated by the plasma Ca++ concentration. An increase in Ca++ concentration of about 10% results in a 2-3-fold increase in the excretion of calcitonin. However, the effect of maintaining strong and prolonged calcium concentration is mainly the effect of parathormone.