DR.MOUAADH ABDELKARIM ASSISTANT PROFESSOR OF PHYSIOLOGY COLLEGE OF MEDICINE KING SAUD UNIVERSITY Thyroid Gland College of Dentistry

Thyroid Gland الغدة الدرقية - Is immediately caudal to the larynx And encircles the anterolateral portion of the trachea - The thyroid is a highly vascular

normally weighing 15 to 20 grams in adults Thyroids hormones profoundly increase the metabolic rate of the body. Complete lack of thyroid secretion usually causes the basal metabolic rate to fall 40 to 50 percent below normal, and extreme excesses of thyroid secretion can increase the basal metabolic rate to 60 to 100 percent above normal.

lactotrophs Thyrotrophs Somatotrophs Corticotrophs Gonadotrophs Thyrotropin-releasing hormone Thyroid-stimulating hormone

Thyroid Gland The thyroid tissue is made up of two types of cells: follicular cells and parafollicular cells. Most of the thyroid tissue consists of the follicular cells, which secrete the iodine-containing thyroid hormones. The parafollicular cells (also called C cells) secrete the hormone calcitonin A follicular lumen is the closed cavity within a follicle of the thyroid glandthyroid

Thyroid hormones – the body’s major metabolic hormone Consist of two closely related iodine-containing compounds: o T 4 – thyroxine (90%) o T 3 – triiodothyronine (10%) Thyroid Hormones

Thyroid hormones are synthesized within thyroid colloid and attached to the protein called thyroglobulin Biosynthesis of Thyroid Hormones

To form normal quantities of thyroxine, about 50 milligrams of ingested iodine in the form of iodides are required each year, or about 1 mg/week. To prevent iodine deficiency, common table salt is iodized with about 1 part sodium iodide to every 100,000 parts sodium chloride. Iodine Is Required for Formation of Thyroxine :

Fate of Ingested Iodides Iodides ingested orally are absorbed from the gastrointestinal tract into the blood in about the same manner as chlorides. Normally, most of the iodides are rapidly excreted by the kidneys, but only after about one fifth are selectively removed from the circulating blood by the cells of the thyroid gland and used for synthesis of the thyroid hormones.

transport of iodides from the blood into the thyroid glandular cells and follicles. The basal membrane of the thyroid cell has the specific ability to pump the iodide actively to the interior of the cell. This is achieved by the action of a sodium-iodide symporter (NIS), which co-transports one iodide ion along with two sodium ions across the basolateral (plasma) membrane into the cell.

The energy for transporting iodide against a concentration gradient comes from the sodium- potassium ATPase pump, which pumps sodium out of the cell, thereby establishing a low intracellular sodium concentration and a gradient for facilitated diffusion of sodium into the cell. >>>> This process of concentrating the iodide in the cell is called iodide trapping.

In a normal gland, the iodide pump concentrates the iodide to about 30 times its concentration in the blood. When the thyroid gland becomes maximally active, this concentration ratio can rise to as high as 250 times. The rate of iodide trapping by the thyroid is influenced by several factors, the most important being the concentration of TSH

STEPS of BIOSYNTHESIS

Thyroid Hormones [T3 - T4] Biosynthesis : by the follicular cells 1- Iodide pump. 2- Thyroglobulin synthesis. 3- Oxidation of iodide to iodine. 4- Iodination of tyrosine, to form mono-iodotyrosine (MIT) & di-iodotyrosine (DIT). 5- Coupling;MIT + DIT = Tri-iodothyronine, ( T3). DIT + DIT = Tetra-iodothyronine, (T4)/ Thyroxine. 6- Release.

T 4 and T 3 bind to thyroxine-binding globulins (TBGs) synthesized by the liver Both bind to target receptors, but T 3 is ten times more active than T 4 Peripheral tissues convert T 4 to T 3 by the enzyme 5’- iodinase Mechanisms of activity are similar to steroids Transport and Regulation of TH

1- T4 & T3 diffuse through the cell membrane. 2- Stored in the targeted tissues (days to weeks). 3- In the nucleus, T3 mainly binds to “thyroid hormone receptor” and influence transcription of genes. Mechanism of action of thyroid hormones

ACTION OF THYROID HORMONES [T3 + nuclear receptors activation of thyroid regulating element on DNA DNA transcription formation of mRNA translation of mRNA specific protein synthesis (target tissue specific)]

RELEASE OF T4 AND T3 TO THE TISSUES

ACTIONS OF THYROID HORMONES

- Is the energy requirement under basal condition (mental and physical rest hours after a meal). - increase oxygen consumption in all tissues except brain. - Increase heat production 1- Basal Metabolic Rate (BMR)

2- Metabolism A) Effect on carbohydrate metabolism: 1- increase glucose uptake by the cells. 2- increase glycogenolysis. 3- increase gluconeogenesis. 4- increase glucose absorption from the GIT.

B) Effects on fat metabolism: 1- increase lipolysis. 2- decrease plasma cholesterol by increase loss in feces. C) Effect on protein metabolism: thyroid hormones stimulate the synthesis as well as the degradation of proteins, whereas in supraphysiological doses protein catabolism predominates 2- Metabolism (Conts.)

The metabolic effects are due to the induction of metabolic enzymes: 1- cytochrome oxidase. 2- NADPH cytochrome C reductase. 3- alpha- glycerophosphate dehydrogenase. 4- malic enzymes. 5- several proteolytic enzymes

3- Effects on the Cardiovascular system: - increase heart rate - increase stroke volume - increase ventilation rate - decrease peripheral resistance * End result is increase delivery of oxygenated blood to the tissues

4- Effects on the CNS: A) Perinatal period: Thyroid hormones are essential for maturation of the CNS. decrease of hormones secretion irreversible mental retardation - Screening is necessary to introduce hormone replacement.

5- Effects on Growth Thyroid hormones act synergistically with growth hormone and IGF to: a) promote bone formation. b) promote ossification. c) promote fusion of bone plate. d) promote bone maturation.

6- Effects on the GIT: 1- increase appetite and food intake. 2- increase of digestive juices secretion. 3- increase of G.I tract motility. excess secretion diarrhea. lack of secretion constipation.

Summary

REGULATION OF HORMONES SECRETION It is regulated by the hypothalamic-pituitary axis.

Diseases of Thyroid Gland, Hyperthyroidism Hyperthyroidism = overactive thyroid o Increased metabolic rate o Enlargement of thyroid gland o Weight loss, nervousness, irritability o Intolerance to heat o Increased cardiac output. o Bulging eyeballs ( Exophthalmos )

Causes of hyperthyroidism Graves Disease Overtreatment with thyroxin Thyroid adenoma (rare) Transient neonatal thyrotoxicosis (Inflammation of thyroid gland)

Hypothyroidism Hypothyroidism = underactive thyroid  2-3 times increase in size ( Goiter )  Slowed metabolic rate, fatigue, weight gain  Cretinism ( physical and mental growth ).  Myxoedema: edematous appearance through out body.

common cause of hypothyroidism Iodine deficiency Auto-immune thyroiditis Thyroidectomy or RAI therapy TSH or TRH deficiency Medications (iodide & Cobalt) Idiopathic

Autoimmune hypothyroidism Hashimoto’s Disease Most common cause of hypothyroidism Autoimmune lymphocytic thyroiditis Antithyroid antibodies: Females > Males Runs in Families!