THYROID GLAND .pdf

Thyroid and Parathyroid glands Physiology

EM Savoeun, MD

ICU Med Khmer Soviet Friendship Hospital (KSFH)

Anatomy

butterfly-shaped thyroid gland is located just inferior to the larynx

right and left lateral lobes About 50% of thyroid glands have a small third lobe,

called the pyramidal lobe normal mass of the thyroid is about 30 g Microscopic spherical sacs called thyroid follicles

Thyroid hormones: thyroxine which is also called tetraiodothyronine or T4 triiodothyronine or T3

A few cells called parafollicular cells or C cells lie between follicles calcitonin, regulate calcium homeostasis.

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Thyroid hormones regulate (1) oxygen use and basal metabolic rate (2) cellular metabolism (3) growth and development.

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Location, blood supply, and histology of the thyroid gland

Hormones of the Thyroid Gland

Thyroxine (T4)

Principle hormone

Increases energy and protein metabolism rate

Triiodothyronine (T3)

Increases energy and protein metabolism rate

Calcitonin

Regulates calcium metabolism

Works with parathyroid hormone and vitamin D

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Thyroid gland stores its secretory product in large quantitiesnormally about a 100-day supply

Synthesis and secretion of T3 and T4 occurs as follows 1. Iodide trapping: Thyroid follicular cells trap iodide

ions (I-)by actively transporting them from the blood into the cytosol

2. Synthesis of thyroglobulin: produced in the rough endoplasmic reticulum and packaged into secretory vesicles undergo exocytosis releases TGB into the lumen of the follicle

Formation, Storage, and Release of Thyroid Hormones

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3. Oxidation of iodide: iodide ions are being oxidized, they pass through the membrane into the lumen of the follicle 2 I- (iodide) I2 (iodine)

4. Iodination of tyrosine: iodine molecules (I2) react with tyrosines one iodine atom yields monoiodotyrosine (MIT or T1), attachment of two iodines produces diiodotyrosine (DIT or T2) TGB with attached iodine atoms stored in the lumen of the thyroid follicle, is termed colloid

5. Coupling of T1 and T2 During the last step in the synthesis of thyroid hormone, two T2 molecules join to form T4, or one T1 and one T2 join to form T3.

Formation, Storage, and Release of Thyroid Hormones

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6. Pinocytosis and digestion of colloid. Droplets of colloid reenter follicular cells by pinocytosis and merge with lysosomes. Digestive enzymes in the lysosomes break down TGB, cleaving off molecules of T3 and T4.

7. Secretion of thyroid hormones: T3 and T4 are lipidsoluble, they diffuse through the plasma membrane into interstitial fluid and then into the blood T4 greater quantity than T3 but T3 is several times more potent after T4 enters a body cell, most of it is converted to T3 by

removal of one iodine

Formation, Storage, and Release of Thyroid Hormones

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8. Transport in the blood. More than 99% of both the T3 and the T4 combine with transport proteins in the blood, mainly thyroxine-binding globulin (TBG).

Formation, Storage, and Release of Thyroid Hormones

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Formation, Storage, and Release of Thyroid Hormones

Thyroid hormones are synthesized by attaching iodine atoms to the amino acid tyrosine. Some of the amino acids in TGB are tyrosines

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Formation, Storage, and Release of Thyroid Hormones

Actions of Thyroid Hormones

Increase basal metabolic rate Regulate development and growth of nervous

tissue and bones Enhance some actions of catecholamines Stimulate lipolysis Stimulate protein synthesis Increase body temperature (calorigenic effect) Stimulate synthesis of Na+/K+ ATPase Increase the use of glucose and fatty acids for ATP

production

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Control of Thyroid Hormone Secretion

Regulation of secretion and actions of thyroid hormones. TRH thyrotropin-releasing hormone, TSH thyroid-stimulating hormone, T3 triiodothyronine, and T4 thyroxine (tetraiodothyronine).

TSH promotes release of thyroid hormones (T3 and T4) by the thyroid gland.

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Control of thyroid gland activity

The hypothalamic-pituitary-thyroid axis controls the thyroid gland function and growth. a. The production and release of thyroid hormone is controlled by thyroid-releasing hormone (TRH) from the hypothalamus.

TRH reaches the anterior pituitary via the portal system, where the thyrotropic cells are stimulated to produce thyroid stimulating hormone (TSH) or thyrotropin. TSH is the only known regulator of thyroid hormone secretion in humans. TSH is released to the systemic blood, by which it travels to the thyroid gland. Here, TSH stimulates the uptake of iodide, and all other processes that promote formation and release of T4 and T3. TSH activates adenylcyclase bound to the cell membranes of the follicular cells and increases their cAMP. T3 has a strong inhibitory effect on TRH secretion, as well as on the expression of the gene for the TRH precursor.

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b. Almost all circulating T3 is derived from T4. TSH also stimulates the conversion of T4 to the more biologically active T3.

Most of the circulating thyroid hormones are bound to plasma proteins, whereby the hormone is protected during transport. There is an equilibrium between the pool of protein-bound thyroid hormone and the free, biologically active forms (T3 and T4) that can enter the body cells. Thyroid hormones are lipid-soluble and they can easily cross the cellular membrane by diffusion.

c. Inside the cell, T3 binds to nuclear receptors and stimulates cellular metabolism and increases metabolic rate. d. The concentrations of T3 and T4 in the blood are recorded by pituitary and hypothalamic receptors.

This negative feedback system keeps the blood concentrations within normal limits, and there is only a minimal nocturnal increase in TSH secretion and T4 release.

Control of thyroid gland activity

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Calcitonin

With respect to regulation of blood Ca2 level, calcitonin and PTH are antagonists

Calcitonin decrease the level of calcium in the blood by inhibiting the action of osteoclasts, the cells that break down bone extracellular matrix.

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The roles of calcitonin (green arrows), parathyroid hormone (blue arrows), and calcitriol (orange arrows) in calcium homeostasis

Calcitonin

Calcitonin is produced by the parafollicular C-cells of the thyroid

Calcitonin inhibits bone resorption by blocking the

parathyroid hormone (PTH)-receptors on the

osteoclasts. The result is an extremely effective lowering

of plasma-Ca2+ and -phosphate. Calcitonin is

important in bone remodelling and in treatment of

osteoporosis.

Calcitonin is a single-chain peptide with a disulphide

ring, containing 32 amino acids. Calcitonin is secreted

from the thyroid gland in response to hypercalcaemia

and it acts to lower plasma [Ca2+], as opposed to the

effect of PTH.

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Administration of calcitonin leads to a rapid fall in

plasma [Ca2+]. Calcitonin is the physiologic antagonist to

PTH and inhibits Ca2+ -liberation from bone (ie, inhibits

both osteolysis by osteocytes and bone resorption by

osteoclasts). But calcitonin reduces plasma phosphate

just as PTH.

Calcitonin probably inhibits reabsorption of

phosphate in the distal tubules of the kidney, but

calcitonin also inhibits the renal reabsorption of Ca2+,

Na+ and Mg2+. Calcitonin may inhibit gut absorption of

Ca2+ and promote phosphate entrance into bone and

cause important bone remodelling.

Calcitonin

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Calcitonin deficiency does not lead to hypercalcaemia, and excess calcitonin from tumours does not lead to hypocalcaemia. Therefore, most effects of calcitonin are evidently offset by appropriate regulation through the actions of PTH and vitamin D

Calcitonin in plasma declines with age and is lower in women than in men. Low levels of calcitonin are involved in accelerated bone loss with age and after menopause (osteoporosis).

Calcitonin protects the female skeleton from the drain of Ca2+ during pregnancy and lactation.

Calcitonin

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Calcitonin is a neurotransmitter in the hypothalamus and in other CNS locations.

Calcitonin is administered to postmenopausal females in attempt to prevent osteoporosis.

Calcitonin

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Disorders of the Thyroid Gland

Goiter is enlargement of thyroid gland Simple goiter

Adenomatous or nodular goiter

Hypothyroidism Infantile hypothyroidism (cretinism)

Hypothyroidism (Hashimotos disease, Goiter)

Myxedema

Hyperthyroidism Graves disease

Thyroid storm

Thyroiditis Hashimoto disease

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Manifestations of Hypothyroid and Hyperthyroid States

Level of Organization Hypothyroidism Hyperthyroidism

Basal metabolic rate Decreased Increased

Sensitivity to catecholamines Decreased Increased

General features

Myxedematous features

Deep voice

Impaired growth (child)

Exophthalmos

Lid lag

Decreased blinking

Blood cholesterol levels Increased Decreased

General behavior

Mental retardation (infant)

Mental and physical sluggishness

Somnolence

Restlessness, irritability, anxiety

Hyperkinesis

Wakefulness

Cardiovascular function Decreased cardiac output

Bradycardia

Increased cardiac output

Tachycardia and palpitations

Gastrointestinal function Constipation

Decreased appetite

Diarrhea

Increased appetite

Respiratory function Hypoventilation Dyspnea

Muscle tone and reflexes Decreased Increased, with tremor and fibrillatory

twitching

Temperature tolerance Cold intolerance Heat intolerance

Skin and hair Decreased sweating

Coarse and dry skin and hair

Increased sweating

Thin and silky skin and hair

Weight Gain Loss 28

Parathyroid Glands

Embedded in thyroid

Parathyroid glands each weigh 3040 mg 4 glands = 120-160mg

Secrete PTH

Increases blood calcium levels

Stimulates osteoclasts

Promotes calcium reabsorption by kidneys

Physiology

Approximately 99% of total body calcium is found in the skeleton and teeth

The remainder is in the extracellular fluids: ionized, protein bound, complexed About 47% of total blood calcium is protein bound,

predominantly to albumin but also to globulins A similar fraction is ionized The remainder is complexed to organic ions such as citrate,

phosphate, and bicarbonate Serum ionized calcium controls vital cellular functions such

as hormone secretion and action, muscle contraction, neuromuscular transmission, and blood clotting

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relationship between parathyroid hormone (PTH) release and the extracellular calcium concentration in

human studies

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Main actions of parathyroid hormone (PTH) and 1,25-(OH)2D in the maintenance of calcium and phosphate homeostasis

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Main actions of parathyroid hormone (PTH) and 1,25-(OH)2D in the maintenance of calcium and phosphate homeostasis

Sequential steps in remodeling of trabecular bone

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Calcitonin and parathyroid hormone (PTH) and their functions related to the maintenance of the blood calcium level

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Regulation of PTH Secretion

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Refferences

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QCM FIN DE COURS

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1. Lhormone de stimulation de la thyrode (TSH) A. Est scrte par lhypothalamus B. Est scrte par le lobe antrieur de lhypophyse C. Stimule la synthse et la libration des hormones thyrodiennes D. Est libre sous laction de la TRH hypothalamique E. Est libre sous laction de lACTH hypothalamique

2. A propos de la synthse des hormones thyrodiennes

A. Loxydation de I- en I2 est une tape clef dans la formation des monoiodotyrosine (MIT) et diiodotyrosine (DIT)

B. La thyroglobuline est synthtise par les cellules folliculaires thyrodiens C. La thyroglobuline ragit avec I2 pour former la tyrosine D. La thyroglobuline iode est stocke dans la lumire des follicules thyrodiens E. La MIT et la DIT sont galement appeles respectivement T3 et T4

3. Le couplage: A. De deux molcules de MIT permet la formation de la thyroglobuline B. De quatre molcules de MIT permet la formation de la thyroxine ou T4 C. De deux molcules de DIT permet la formation de la thyroxine ou T4 D. De trois molcules de MIT permet la formation de la triiodothyronine ou T3 E. Dune molcule de MIT et dune molcule de DIT permet la formation de T3

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4. A propos des hormones thyrodiennes T3 et T4: A. Leur transpot sanguin ncessite landrogen binding protein (ABP) B. T4 peut tre convertie, dans les tissus priphriques, en T3 C. T4 peut tre convertie, dans les tissus priphriques, en T3 inverse qui est

active D. T3 est biologiquement plus active que T4 E. T4 est biologiquement plus active que T3

5. A propos de la rgulation de lactivit thyrodienne: A. TSH inhibe la scrtion de T3 et T4 par effet direct sur les follicules

thyrodiens B. T3 et T4 activent par rtroaction positive la scrtion de TSH par lhypophyse C. T3 et T4 activent par effet rtroaction positive la scrtion de TRH par

lhypothalamus D. T3 et T4 inhibent par effet rtroaction ngative la scrtion de TSH par

lhypophyse E. TSH active la synthse et la libration de T3 et T4 par les cellules folliculaires.

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7. Les hormones thyrodiennes T3 et T4: A. Jouent un rle important dans lossification B. Agissent en synergie avec la somatotrophine C. Augmentent la ventilation pulmonaire D. Augmentent le dbit cardiaque E. Diminuent la VO2

8. Lhyperthyrodie: A. Provoque une augmentation du mtabolisme basal B. Est caractrise par un taux sanguin lev de TSH C. Provoque une augmentation de la production de chaleur D. Est observe chez le sujet atteint de la maladie de Basedow E. Na pas de consquence majeure sur le mtabolisme

6. Les scrtions thyrodiennes de T3 et T4 sont: A. Stimules par la TSH B. Stimues par des immunoglobulines de stimulation de la thyrode C. Eleves dans la maladie de Basedow D. Fortement stimules par des immunoglobulines chez les patients atteints de

maladie de Basedow E. Inhibes par des immunoglobulines chez les patients atteints de maladie de

Basedow

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10. Lhypothyrodie: A. Perturbe le bilan azot B. Augmente la frquence cardiaque C. Diminue le dbit cardiaque D. Est caractrise par le myxoedme et le goitre E. Na pas de consquence majeure sur le mtabolisme.

9. Lhypothyrodie: A. Provoque une augmentation du mtabolisme basal B. Est caractrise par un taux sanguin faible de TSH C. Provoque une augmentation du dbit sanguin D. Est observe chez le sujet atteint de la maladie de Basedow E. Est traite par administration dhormone thyrodiennnes

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1. La PTH (hormone parathyrodienne) A. Rgule le taux de calcium srique B. Est synthtise et scrte par les cellules folliculaires thyrodiennes C. Est synthtise par les cellules folliculaires thyrodiennes, stocke et libre par

les parathyrodes D. Provoque une augmentation du calcium srique E. Provoque une augmentation du phosphate srique

2. Parmis les facteurs suivants lesquels jouent un rle dans la rgulation du calcium srique? A. La PTH B. LACTH C. La vitamine D D. La calcitonine E. La TSH

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3. La PTH (hormone parathyrode): A. Est scrte suite une diminution du calcium srique B. Diminue la rabsorption rnale de calcium C. Augmente la rsorption osseuse D. Diminue la rabsorption rnale des phosphates E. Diminue la rsorption osseuse

4. Parmi les facteurs suivants lesquels provoquent une augmentation de la rsorption osseuse? A. La PTH B. LACTH C. La vitamine D D. La calcitonine E. La TSH

5. En cas dhyperparathyrodie, il y a: A. Augmentation des taux sriques de calcium et de phosphates B. Diminution des taux sriques de calcium et de phosphates C. Augmentation de la phosphaturie D. Diminution de la rsorption osseuse E. Augmentation de la rsorption osseuse

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6. A propos de la vitamine D: A. Sa carence chez lenfant provoque le rachitisme B. La production de sa forme active (1,25-dihydroxycholcalcifrol) est stimule par

la PTH C. Elle est dgrade par la 1-hydroxylase D. Elle a une action synergique avec la calcitonine, sur la rsorption osseuse E. Sa scrtion est stimule par la diminution du calcium srique

7. Parmi les facteurs suivants lesquels provoquent une augmentation de la rabsorption rnale du calcium? A. La PTH B. LACTH C. La vitamine D D. La calcitonine E. La TSH

8. En cas dhypoparathyrodie, il y a: A. Augmentation des taux sriques de calcium et de phosphates B. Diminution du taux srique de calcium et ttanie C. Augmentation du taux srique de phosphates D. Diminution du taux srique de phosphates E. Augmentation de la phosphaturie

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9. La calcitonine: A. Est scrte sous leffet dune augmentation du taux de calcium srique B. Diminue la rsorption osseuse C. A pour action majeure une augmentation de la rabsorption rnale du

phosphate D. A pour action majeure une augmentation de la rabsorption rnale du calcium

via la vitamine D E. A pour action majeure une augmentation de labsorption intestinale du calcium

via la vitamine D

10. Quelle est la proposition qui provoquent une augmentation de labsorption intestinale du calcium: A. La PTH et lACTH B. LACTH et la vitamine D C. La vitamine D et la PTH D. La calcitonine, la vitamine D et la PTH E. La calcitonine et la vitamine D