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.

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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Formation, Storage, and

Release of Thyroid Hormones
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
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Formation, Storage, and

Release of Thyroid Hormones
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 T2molecules join to
form T4, or one T1 and one T2join to form T3.

Formation, Storage, and

Release of Thyroid Hormones
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
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Formation, Storage, and

Release of Thyroid Hormones
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

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

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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Control of thyroid gland activity

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.
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Calcitonin
Calcitonin decrease the level of calcium in the blood by inhibiting the action of
osteoclasts, the cells that break down bone extracellular matrix.
The roles of calcitonin (green arrows),
parathyroid hormone (blue arrows), and
calcitriol (orange arrows) in
calcium homeostasis

With respect to regulation of blood Ca2 level,

calcitonin and PTH are antagonists

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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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Calcitonin
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.
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Calcitonin
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.
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Calcitonin
Calcitonin is a neurotransmitter in the hypothalamus and in
other CNS locations.
Calcitonin is administered to postmenopausal females in
attempt to prevent osteoporosis.

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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

Myxedematous features
Deep voice
Impaired growth (child)

Exophthalmos
Lid lag
Decreased blinking

Increased

Decreased

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

Hypoventilation

Dyspnea

Decreased

Increased, with tremor and fibrillatory

twitching

Cold intolerance

Heat intolerance

Decreased sweating
Coarse and dry skin and hair

Increased sweating
Thin and silky skin and hair

Gain

Loss

General features
Blood cholesterol levels
General behavior

Respiratory function
Muscle tone and reflexes

Temperature tolerance
Skin and hair
Weight

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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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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
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
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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
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.

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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

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