Physiology of The Thyroid Gland

M. Djauhari Widjajakusumah
Department of Physiology
Fakultas Kedokteran Universitas Indonesia

THE THYROID GLAND

One of the largest endocrine gland

Consists of two lobes lie on either side of

the trachea

Highest blood flow rates of any tissue in the

body

Tremendous capacity for growth:

appropriate stimulus
greatly
enlarged (goiter/struma)

Figure 181.
Ganongs Review of Med Physiol
22th ed, 2006

THE THYROID GLAND

Made up of multiple acini (follicles)

Each spherical follicle

is surrounded by a single layer of

cells
is filled with protein-containing
material: colloid, which major
component is thyro-globulin that
serves as the precursor of thyroid
hormones.

Ganongs Review of Med Physiol 22th ed, 2006

Ganongs Review of Med Physiol 22th ed,

THE THYROID GLANDS

FOLLICLES

Inactive gland:
the colloid is abundant
the follicles are large
the lining cells are flat

Active gland:
the edge of the colloid is scalloped:
forming reabsorption lacunae
follicles are small
lining cells are cuboid or columnar
Ganongs Review of Med Physiol 22th ed,
2006

THE MAIN FUNCTIONS OF THYROID

HORMONES

Maintain the level of metabolism in the

tissues for their normal function

Stimulate the O2 consumption of most cells

in the body

Help regulate lipid and carbohydrate

metabolism

Necessary for normal growth and maturation

FROM IODIDE TO THYROID

CIRCULATING HORMONES

Trapping

Iodide Hormone Synthesis:

oxidation
iodination
coupling reaction (oxidative condensation)

Hormone Secretion

Outline of thyroid hormone biosynthesis. Iodination of tyrosine takes place at the

apical border of the thyroid cells while the molecules are bound in peptide linkage in
thyroglobulin.

Plasma

I-

I-

Thyroid
cell

Active
transport

Thyro-globulin
molecule

Colloid
Oxidation
(Thyroid peroxidase)
II
Iodide Iodine

I-

Monoiodotyrosine (MIT)
Diiodotyrosine (DIT)

MIT +DIT
DIT +MIT

Tyrosine

Alanine+
Alanine+

DIT +DIT

Triiodothyronine (T3)
Reverse Triiodothyronine
(RT3)
Alanine+

Thyroxine (T4)

IODIDE TRAPPING

Iodide active transport from circulation to the

colloid

Stimulated by Thyroid Stimulating Hormone (TSH)

Iodide is pumped into the cells against the

electrical gradient (resting membrane potential 50 mv)
iodide pump (competitively
inhibited by perchlorate and other anions)

Iodide then diffuses down the electrical gradient

into the colloid

HORMONE SYNTHESIS

Oxidation (thyroid peroxidase):

Iodide is oxidized to iodine

Iodination (thyroid peroxidase; blocked by

propylthiouracil)
binding of iodine to thyrosine-thyroglobulin
Mono-iodotyrosine (MIT)
binding of iodine to MIT
Di-iodotyrosine (DIT)

Coupling reaction / oxidative condensation

(thyroid peroxidase))

MIT + DIT

Tri-iodothyronine (T3)

DIT + DIT
(T4)

Tetra-iodothyronine/Thyroxine

HORMONE SECRETION

(1) Colloid (with all its contents) ingestion /

endocytosis
reabsorption lacunae
(2) Endocytotic vacuoles of colloid merge with
lysosome (protease):
peptide bonds between iodinated tyrosine and
thyroglobulin are broken
free T4, free T3,
free DIT and free MIT are liberated

HORMONE SECRETION

(3) Iodinated tyrosine (DIT, MIT) are

deiodinated by iodotyrosine deiodinase
free iodine and tyrosine-thyroglobulin
compounds are liberated, and are
reutilized.
(4) Free T3 and free T4 pass into the
circulation

Secretion and interconversion of thyroid hormones in normal adult humans.

Figures are in micrograms per day. Note that most of the T3 and RT3 are formed
from T4 deiodination in the tissues, and only small amounts are secreted by the
thyroid.

THE AVARAGE DISTRIBUTION OF IODINATED

COMPOUNDS IN THE NORMAL HUMAN THYROID

MIT 23 %
DIT 33 %
T4 35 %
T3 7 %
(Ganong Review of Medical Physiology 21st ed. 2003)

PLASMA LEVELS OF THYROID HORMONES

Total plasma T4 : 8 ug/dL (103 nmol/L)

Total plasma T3 : 0.15 ug/dL (2.3 nmol/L)

Large amount of both are bound to plasma

proteins (Protein-Bound Iodine / PBI)
PBI - T4 : 7.998 ug/dL (99.98 %)
free T4 : 0.002 ug/dL ( 0.02 %)
PBI - T3 : 0.15 ug/dL
(99.98 %)
free T3 : 0.0003ug/dL ( 0.02%)

PLASMA PROTEINS THAT BIND THYROID HORMONES

(1) Albumin (TBA)
13%

3500 mg/dL

PBI - T4

PBI - T3 53%
(2) Prealbumin (TBPA)

(3) Globulin (TBG)

67%

15 mg/dL PBI - T4 20%

PBI - T3 1%
2 mg/dL

PBI - T4

PBI - T3 46%

Distribution of T4 in the body. The distribution of T3 is similar.

The dashed arrow indicates inhibition of TSH secretion by
increases in the free T4 level in ECF. Approximate concentrations
in human blood are shown in parentheses.

Temprature
regulatory
centers

Environmental
Influences

Other brain
centers

Hypothalamus

(-)

(-)
TRH

Anterior pituitary

(-)

TSH
Iodide

Thyroid gland
T3 & T4

Heat production

Biological effects

Metabolism of CH, proteins,

and fats

Primary steps
involved in
regulating thyroid
hormone
production

REGULATION OF THYROID SECRETION

Hiypothalamus - Hypophysis - Thyroid axis

Feed back mechanisms

Environmental influences:
Temperature
Stress

EFFECTS OF THYROID HORMONES

(1) Calorigenesis
(2) Increase cardiac output
(3) Increase oxygenation
(4) Effects on carbohydrate metabolism
(5) Effects on lipid metabolism
(6) Effects on protein metabolism
(7) Promote normal growth
(8) Promote development and maturation of nervous
system

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Calorigenic Action

Increase O2 consumption of metabolically

active tissues, except adult brain, testes,
uterus, lymph nodes, spleen, and anterior
pituitary.

Some effect is due to fatty acids

metabolism.

Increase membrane-bound Na+-K+ ATPase

activity.

PHYSIOLOGIC EFFECTS OF THYROID

HORMONES

Effects Secondary to Calorigenesis

Increased nitrogen excretion: endogenous protein

and fat stores catabolism weight loss (if food
intake is not increased).

Large doses of thyroid hormones:

extra heat production slight increase in

body temperature heat dissipating
mechanism cutaneous vasodilatation
decreased peripheral resistance.
thyroid hormones + catecholamines
increased cardiac output + cardiac rate,
shortened circulation time.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Effects Secondary to Calorigenesis

Large doses of thyroid hormones:
increased need for vitamins precipitation of
vitamin deficiency.

Small / low doses of thyroid hormones:

decreased hepatic carotene conversion to vitamin A
carotenemia yellowish tint of the skin (without
yellow scleras).
accumulation of skin proteins combined with
polysaccharidas, hyaluronic acid, and chondrotin
sulfuric acid water retention and puffiness of the
skin (myxedema).
decreased milk secretion.
abnormalities in menstrual cycle and fertility.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Effects on the Nervous System

Probably are secondary to increased responsiveness to

catecholamines increased activation of the reticular
activating system.

Brain development: cerebral cortex and basal ganglia,

and cochlea hypothyroidism during development:
mental retardation, motor rigidity, deaf-mutism.

Slow mentation and elevated CSF protein in

hypothyroidism.

Rapid mentation, irritability and restlessness in

hyperthyroidism.

Brain converts T4 to T3.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Relation to Catecholamine

Intimate interrelated action of thyroid hormones and

catecholamines.

Increased metabolic rate effect, stimulation effects

on nervous system, cardiovascular effects of
epinephrine are similar to those of thyriod
hormones.

Catecholamines toxicity is markedly increased when

treated with T4.

Hyperthyroidism sign and symptom (cardiovascular,

tremulousness, sweating) are abolished by
sympathectomy, and reduced by drugs that block
beta-adrenergic receptors (e.g. propranolol).

Beta blockers are used in thyrotoxicosis treatment.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Effects on the Heart

Increased number and affinity of beta-adrenergic

receptors in the heart increase its sensitivity to
inotropic and chronotropic effects of catecholamines.

Increased number of alpha-MHC (myosin heavy chain)

in the atria.

Effects on Skeletal Muscle

Increased protein catabolism in skeletal muscle

muscle weakness (thyrotoxic myopathy) in
hyperthyroidism.

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Effects on Carbohydrate Metabolism

Increased carbohydrate absorption from gastrointestinal

tract in hyperthyroidism: rapid rise in the plasma glucose
level after a carbohydrate meal, sometimes exceeding the
renal threshold.

Effects on Cholesterol Metabolism

Increased formation of LDL receptors in the liver

increased hepatic removal of cholesterol from the
circulation lower circulating cholesterol levels before the
metabolic rate rises (independent of the stimulation of O2
consumption).

PHYSIOLOGIC EFFECTS OF THYROID HORMONES

Effects on Growth

Essential for normal growth and skeletal maturation

Necessary for the normal growth hormone secretion

Potentiate the effect of growth hormone on the tissue

In hypothyroid children, bone growth is slowed and

epiphysial closure is delayed.

THE THYROID HORMONES

Hyposecretion causes:

mental and physical slowing

poor resistance to cold

in children: mental retardation and dwarfism

Hypersecretion leads to:

body wasting

nervousness

tachycardia

tremor

excess heat production

HYPERTHYROIDISM

Excess secretion of thyroid hormones

Increased heart rate

Weight loss

Highly responsive to stimuli

HYPOTHYROIDISM

Deficiency in thyroid hormones production

Defect in
Thyroid gland itself, hypopthalamus, hypophysis

Slower metabolic rate

Reduced rate of heat production

Intolerance to cold temprature

Myxedema

Decreased cardiac output

Slowing of intellectual functions

Lethargy

Speech impairment

Thank You