Endocrinol Pred 04

The thyroid gland is one of the largest endocrine glands, weighing about 20 g in the adult human. It consists of right & left lobes that lie below the larynx on either sides of and anterior to the trachea. The two lobes are connected by a thin tissue known as isthmus.

It is composed of a large number of follicles, each is made of a single layer of epithelium (simple cuboidal epithelium) surrounding a central lumen filled with a substance called colloid (glycoprotein called thyroglobulin). In between the follicles, there are other cells called parafollicular cells which secrete calcitonin hormone (polypeptide of 32 amino acids).

Thyroid hormones Folicular cells of thyroid gland secretes two iodine containing hormones which are: 1- Thyroxine (tetraiodothyronine) (T4) 2- Triiodothyronine (T3)

Synthesis, storage &release of thyroid hormones 1- Thyroglobulin synthesis:

Thyroglobulin is synthesized within the follicular cells, then passes into the lumen, where it is stored as a part of the colloid.

2- Iodide pump:

Iodide (I¯) (the ionic form of iodine) in food and drinking water is absorbed from the gastrointestinal tract into the blood, which are then actively transported into thyroid cells against concentration gradient (iodide pump).

Synthesis, storage &release of thyroid hormones 3- Iodide oxidation: (continue) Iodides are then diffused into the lumen, where it is oxidized to iodine .

4- Formation of thyroid hormones: a- Iodination: The free iodine is then attached to tyrosine to form monoiodotyrosine (MIT). A further iodination of MIT gives diiodotyrosine (DIT). b- Coupling: The coupling of two iodinated tyrosines. If DIT + DIT are coupled → T4 But if DIT + MIT are coupled → T3

Synthesis, storage &release of thyroid hormones (continue) 5- Storage of thyroid hormones:

The formed T4 and T3 are then stored in the follicular lumen and not in the intracellular fluid (in contrast to other hormones). Note that, T4 and T3 are not free, but still present as part of the thyroglobulin molecules.

6- Release of thyroid hormones:

When the follicular cells are stimulated to produce thyroid hormones (by TSH), a colloid portion (containing thyroglobulin) is taken into the follicular cells and broken down by proteolytic enzymes to produce free T4 and T3, which then diffuse into the blood stream.

Notes The plasma level is about 8 μ g/dl of T4 & about 0.15 μ g/dl of T3 (with a ratio of T4 to T3 is 50:1). Thyroxine (T4) is converted to the active T3 Most of the thyroid hormones circulating in the blood are bound to transport proteins. Only a very small fraction of the circulating hormone is free (unbound) and biologically active, hence measuring concentrations of free thyroid hormones is of great diagnostic value.

1- Metabolic effects: Thyroid hormones exert numerous metabolic effects in almost all tissues of the body.

a- The metabolic rate:

Thyroid hormones increase the basal metabolic rate, through increasing O2 consumption and heat production.

b- Carbohydrate metabolism:

Thyroid hormones increase blood concentration, through stimulation of: (1) Intestinal glucose absorption, (2) Glycogenolysis and (3) Gluconeogenesis.

glucose

1- Metabolic effects:

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c- Lipid metabolism:

Thyroid hormones increase lipid mobilization from adipose tissue (lipolysis) and further increase fatty acids oxidation.

d- Protein metabolism:

Thyroid hormones (at normal physiological concentration) increase protein synthesis (anabolic effect) due to stimulation of mRNA formation. However, when thyroid hormones are present in excess, they cause a decrease in protein synthesis and an increase in protein breakdown, which result in muscle weakness and body weight loss.

2- Growth effects (physical & mental activities):

Thyroid hormones are essential for all growth processes during the early postnatal periods, where adequate hormone amounts are needed for both: (a) Physical growth and (b) Mental development. This achieved by: Stimulation of growth hormone secretion anterior pituitary gland and Promotion of IGF-I production by the liver.

3- Other effects:

by

a- Cardiovascular system: Increase cardiac output through increasing of the rate and strength of cardiac contraction.

3- Other effects:

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b- Respiratory system: Increase the rate and depth of respiration i.e. increase utilization of oxygen and formation of carbon dioxide.

c- Reproductive system: Thyroid hormones are necessary for normal reproductive functions (due to the metabolic effects of the thyroid hormones). Also, thyroid hormones increase milk synthesis in lactating women.

I- Hypothyroidism (thyroid hypofunction) A- Cretenism: If begins after birth and continues throughout childhood leads to cretinism. This is characterized by: (1) Reduced skeletal and nervous maturation, so the cretin individuals may not exceed one meter in height (dwarf) (2) Delayed or stopped of sexual maturation. (3) Low metabolic rate with increased feeling of cold and the cretin is usually obese.

I- Hypothyroidism (thyroid hypofunction) B- Myxedema: This is the condition of hypothyroidism in adults. It is characterized by: (1) Low metabolic rate and reduced heat production, with increased feeling of (2)cold. Body weight is increased, with accumulation of mucoproteins under the skin, giving edematous appearance that is most evident in (3) Increased blood lipids, the face. particularly cholesterol, leading to atherosclerosis. (4) Slow heart rate. (5) Depressed reproductive functions.

II- Hyperthyroidism (thyrotoxicosis): Toxic joiter:

It is mostly result from the development of thyroid tumor. Symptoms: (1) Increased metabolic rate with increased feeling of warmth. (2) Increased sweating (due to increased heat loss). (3) Body weight loss and muscular weakness. (4) Hyperglycemia and decreased blood lipids. (5) Increased cardiac output, excitability nervousness.

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II- Hyperthyroidism (thyrotoxicosis): Grave’s disease: Is a condition in which toxic goiter is associated with exophthalmos (eye ball protrusion). The cause of protruding eyes is a hormonal substance called exophthalmos-producing substance, which is secreted by the anterior pituitary in some hyperthyroid patients (about 30%) instead of TSH.

II- Hyperthyroidism (thyrotoxicosis): Simple Goiter: It is caused in response to deficiency in dietary iodine. So, the lack of iodine leads to lowered thyroid hormones and raised TSH, which stimulates thyroid gland to secrete large amounts of thyroglobulin, but increased thyroid hormones production does not occur, (due to iodine lack). Therefore, the follicles become enlarged in size with normal activity. Simple goiter may be due to the increased thyroid hormone requirement at puberty or during pregnancy or lactation.