Thyroid and Parathyroid glands

Physiology
EM Savoeun, M.D.
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.
2
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

3
 Histology

Functional unit of thyroid gland – Acinus or thyroid follicle

4
Thyroid Hormones

5
 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

6
 Hormones in circulation
• Strongly bound to serum proteins
• Bound to (in decreasing order of affinity)
– Thyroxine Binding Globulin
– Thyroxine Binding Pre Albumin
– Serum Albumin
• Drugs competing with binding
– Salicylates
– Hydantoins
– Diclofenac
7
 Free Thyroid Hormones
• Majority of cells cannot take up in bound form
• Normal individuals – Total thyroid hormones mirror the
free hormones
• States of elevated Thyroxine Binding Globulins
– Pregnancy
– Estrogen therapy and oral contraceptives
– Hypothyroidism
• States of decreases Thyroxine Binding Globulins
– Proteins malnutrition
– Cirrhosis
– Androgen
– Acute and chronic illness
– Hyperthyroidism
8
 Thyroid Hormones
Hormones T4 T3
property Serum concentration
Total Hormone 8 g / dl 0.14 g / dl
Fraction of total
hormone in the free 0.02% 0.3%
form
Serum half-life 7 days 0.75 day
Relative metabolic
0.3 1
potency

9
Synthesis of thyroid hormones
Iodide Trapping

Formation and secretion of Thyroglobulin (TG)

Oxidation of iodide ions

Organification of Thyroglobulin (TG)

Storage of Thyroglobulin (TG)

Release of Thyroid Hormones: T4 & T3

10
 Formation, Storage, and
Release of Thyroid Hormones
• Thyroid gland stores its secretory product in
large quantities—normally about a 100-day
supply
• Synthesis and secretion of T3 and T4 occurs as
follows:

11
1. Iodide trapping: Thyroid follicular cells trap iodide
ions [I-] by actively transporting them from the blood
into the cytosol

Colloid

12
Factors affecting iodide [I-] uptake
• Enhancers
– TSH
– Iodine deficiency
– TSH receptor antibodies
– Autoregulation
• Inhibitors
– I- excess
– Cardiac glycosides (Digoxin, Ouabain)
– Perchlorate
– Bromides and Nitrates
13
 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 and
Secretion of TG

14
 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

Oxidation of
Iodide Ions &
Iodination of TG

15
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

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

16
7. Secretion of thyroid
hormones: T3 and T4 are lipid
soluble, 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
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).
TSH
17
 Stimulators of T4 and T3 release
• TSH
• VIP (vasoactive intestinal peptide)
• -adrenergic agonists
• Long-Acting Thyroid Stimulators (LATS) /
Thyroid Stimulating Immunoglobulins (TSI)
• Low temperature

18
Regulation of Thyroid Hormones

19
Effects of TSH on Thyroid Gland

20
Physiological Effects of Thyroid
Hormones

21
Effect of Thyroid Hormones

22
 Metabolic Actions
Calorigenic Action Mitochondria Cell membrane Growth
 Heat production  Size  Na – K ATPase Brain during fetal
enzyme life and for 1st few
years
 BMR  Number General growth in
later age
 Food utilization
 ATP formation

23
 Metabolic Actions
Carbohydrate Proteins Fats Vitamins
 Rapid uptake of Physiological dose  Fat Stores  Requirement
glucose by cells is anabolic
Glycolysis Pharmacological  Free fatty acid Hepatic conversion
dose is catabolic concentration in the of carotene to Vit. A
plasma
 Gluconeogenesis Mobilizes bone Oxidation of FFA
protein
 Rate of
absorption
Insulin secretion

24
 Action on specific organ systems
CVS RS GIT CNS
 Rate  Rate  Appetite Cerebration
 Contraction  Depth of  Food intake
respiration
 Blood flow  Secretion of
digestive juices
 Cardiac output  Motility of the
GIT

25
 Action on specific organ systems
Sleep Muscles Endocrine Reproductive
Excitable synapses Slight increase in PTH Normal sexual
So difficult to sleep thyroid hormones development
muscles react
vigorous
If excess Muscle Steroids from Normal menstrual
Weakens adrenals cycle
Fine muscle tremor Insulin from islets Fertility
due to increased
reactivity of the
neuronal synapses
Less TH then
sluggish muscles,
slow relaxation
after contraction

26
 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.
27
28
29
30
31
 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),

With respect to regulation of blood Ca2+ level,
parathyroid hormone (blue arrows), and
calcitonin and PTH are antagonists
calcitriol (orange arrows) in
calcium homeostasis

32
 Calcitonin
Calcitonin is produced by the parafollicular C-cells of the
thyroid
 Calcitonin is a single-chain peptide with a disulphid ring,
containing 32 amino acids.
• Inhibits bone resorption by blocking the parathyroid hormone (PTH)-
receptors on the osteoclasts
• Lowering of plasma-Ca2+ and -phosphate
• Calcitonin is important in bone remodelling and in treatment of
osteoporosis.
• 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.

33
 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).
 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. 34
 Calcitonin
• Calcitonin deficiency does not lead to hypercalcaemia,
and excess calcitonin from tumours does not lead to
hypocalcaemia
• 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.

35
 Calcitonin
 Calcitonin is a neurotransmitter in the hypothalamus and in
other CNS locations.
 Calcitonin is administered to postmenopausal females in
attempt to prevent osteoporosis.

36
37
 Disorders of the Thyroid Gland
• Goiter is enlargement of thyroid gland
– Simple goiter
– Adenomatous or nodular goiter
• Hypothyroidism
– Infantile hypothyroidism (cretinism)
– Hypothyroidism (Hashimoto’s disease, Goiter)
• Myxedema
• Hyperthyroidism
– Graves disease
– Thyroid storm
• Thyroiditis
– Hashimoto disease

38
39
 Manifestations of Hypothyroid and
Hyperthyroid States
Level of Organization Hypothyroidism Hyperthyroidism
Basal metabolic rate Decreased Increased
Sensitivity to catecholamines Decreased Increased
Myxedematous features Exophthalmos
General features Deep voice Lid lag
Impaired growth (child) Decreased blinking
Blood cholesterol levels Increased Decreased
Mental retardation (infant) Restlessness, irritability, anxiety
General behavior Mental and physical sluggishness Hyperkinesis
Somnolence Wakefulness
Decreased cardiac output Increased cardiac output
Cardiovascular function
Bradycardia Tachycardia and palpitations
Constipation Diarrhea
Gastrointestinal function
Decreased appetite Increased appetite
Respiratory function Hypoventilation Dyspnea
Decreased Increased, with tremor and fibrillatory
Muscle tone and reflexes
twitching
Temperature tolerance Cold intolerance Heat intolerance
Decreased sweating Increased sweating
Skin and hair
Coarse and dry skin and hair Thin and silky skin and hair
40
Weight Gain Loss
Parathyroid Glands

• Embedded in thyroid
• Parathyroid glands each
weigh 30–40 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

42
43
 relationship between parathyroid hormone (PTH)
release and the extracellular calcium concentration in
human studies

44
Main actions of parathyroid
hormone (PTH) and 1,25-(OH)2D
in the maintenance of calcium and
phosphate homeostasis

45
Main actions of parathyroid hormone (PTH)
Sequential steps in remodeling of
and 1,25-(OH)2D in the maintenance of
trabecular bone
calcium and phosphate homeostasis

46
Calcitonin and parathyroid hormone (PTH) and their functions
related to the maintenance of the blood calcium level

47
48
Refferences

49