TRANSPORT & METABOLISM

THYROID HORMONES
Synthesis of Thyroid Hormone
 Percentage Distribution

The human thyroid secretes about 80micro g (103 nmol)

Of T4 ,4micro g (7nmol) of T3, and 2micro g (3.5 nmol) of RT3 per
day
 Activation And Degradation Of
Thyroid Hormone
• Normally about 40% of T4
is deiodinated in to T3 and
remaining 60% in to rT3.
• During foetal life, prolonged
starvation, and
glucocorticoid use >60% T4
is converted in to rT3
• On other hand in obesity T3
production is greater than
the amount of rT3
Three different deiodinases act on thyroid
hormones: D1, D2, and D3 .

All are unique in that they contain the rare amino

acid selenocysteine, with selenium in place of sulfur,
which is essential for their enzymatic activity.

D1 is present in high concentrations in the liver,

kidneys, thyroid, and pituitary. It appears primarily
to be responsible for monitoring the formation of T 3
from T4 in the periphery.
D2 is present in the brain, pituitary, and brown fat. It also
contributes to the formation of T3. In the brain, it is located in
astroglia and produces a supply of T3 to neurons.

D3 is also present in the brain and in reproductive tissues. It

acts only on the 5 position of T4 and T3 and is probably the
main source of RT3 in the blood and tissues.

Overall, the deiodinases appear to be responsible for

maintaining differences in T3/T4 ratios in the various tissues in
the body.

In the brain, in particular, high levels of deiodinase activity

ensure an ample supply of active T3.
 Transport
• both hormones are bound to plasma proteins
– measured directly by radioimmunoassay
– has replaced protein-bound iodine etc. as an index
• proteins which bind thyroid hormones include,
– albumin
– thyroxine-binding prealbumin (TBPA)
– thyroxine binding globulin (TBG)
• TBG resides between a1 & a2-globulin
• albumin has the highest capacity to bind T4
– however affinities  most T4 is bound to TBG
 Thyroid Hormone Binding
Protein Conc’n Half-life T4 T3
(mg/dl) (days) binding % binding %
Albumin 3500 13 13 53
TBG 2 5 67 46
TBPA 15 2 10 1

Normal Plasma level: 8.0 g/dl 0.15 g/dl

Total percentage bound: 99.98% 99.8%
Plasma free hormone concentration: 2 ng/dl 0.3 ng/dl
 TRANSPORT OF THYROID
HORMONES IN BLOOD

• Equilibrium between
Bound and Free
Circulating Thyroid
Hormone
The normal total plasma T 4 level in adults is
approximately 8 micro  g/dL (103 nmol/L), and the
plasma T3 level is approximately 0.15 micro  g/dL (2.3
nmol/L).

T4 and T3 are relatively lipophilic; thus, their free

forms in plasma are in equilibrium with a much larger
pool of protein-bound thyroid hormones in plasma
and in tissues.
It is the free thyroid hormones
in plasma that are
physiologically active and that
feed back to inhibit pituitary
secretion of TSH
 Binding of Hormones
• Serves to prevent renal loss of hormones
• Constitute reservoir for the supply of free
hormones
 TRANSPORT OF THYROID
HORMONES IN BLOOD

• T4 has the higher affinity for binding

proteins; therefore, it binds more tightly to
protein than T3 does,
• The half-life of T4 is greater than that of
T3
– T4 half-life = 6 days
– T3 half-life = 1 day
• Most circulating thyroid hormone is T4.
• Tight binding of T4 with plasma proteins is
shown by it’s prolonged half life @6-7 days.

• The half life of T3 is @1 day, due to it’s

lesser affinity for plasma proteins.
Fluctuations in Binding
When a sudden, sustained increase in the
concentration of thyroid-binding proteins in the
plasma takes place, the concentration of free
thyroid hormones falls.

This change is temporary, because the decrease

in the concentration of free thyroid hormones in
the circulation stimulates TSH secretion, which
in turn causes an increase in the production of
free thyroid hormones
Functions of the Thyroid Hormones

It is likely that all cells in the body are targets for

thyroid hormones. While not strictly necessary
for life, thyroid hormones have profound effects
on many "big time" physiologic processes, such
as development, growth and metabolism.
Physiologic Actions Of Thyroid
Hormones
 Thyroid Hormone:
Functions
• Thyroid Hormones Increase the
Transcription of Large Numbers of
Genes
• Enhance variety of protein synthesis
(protein enzymes, structural proteins,
transport proteins, and others)
• The net result is generalized increase in
functional activity throughout the body.
 Physiologic Actions Of Thyroid
Hormones

• Metabolic Rate
– Thyroid hormones increase metabolic rate.
– Thyroid hormones increase the activity of the
membrane-bound Na/K-ATPase in many
tissues.
Effect of Thyroid Hormone on Cellular
Metabolic Activity

The thyroid hormones increase the metabolic

activities of all or almost all the tissues of the
body. The basal metabolic rate can increase to as
much as 60 to 100 per cent above normal when
large quantities the hormones are secreted. The
rate of utilization of foods for energy is greatly
accelerated .
 Calorigenic Action
• T3 & T4  VO2 in all tissues, except,
– adult brain
– testes
– uterus
– spleen & lymph nodes
– anterior pituitary (actually decreases)
 Physiologic Actions Of Thyroid
Hormones

Growth and Maturation

Brain:
– Without adequate thyroid hormones during the
peri-natal period ( After birth), abnormalities
rapidly develop in nervous system
maturation.
– These abnormalities lead to mental
retardation.
– These neural changes are irreversible unless
replacement therapy is started soon after birth.
 Effect on Nervous System
• Necessary for normal development and
activity of nervous systemas it helps in:
• Myelination of axons
• Branching of dendrites
• blood supply to neurons
• T4 deficiency after birth Infantile Brain
• MENTAL RETARDATION
Effect of Thyroid Hormone on Development and
Growth

• Stimulation of skeletal growth in childhood. In

those who are hypothyroid, the rate of growth is
greatly retarded.

• Promotion of normal brain development in the

early postnatal period. Those who are
hypothyroid will remain mentally deficient
throughout life.
 Physiologic Actions Of Thyroid
Hormones

• Permissive nature of thyroid hormones:

– Different hormones function properly only
when normal amounts of thyroid hormones
are present.
– In absence of Thyroid hormones other
hormones can’t function properly.
 Physiologic Actions Of Thyroid
Hormones
Growth:
• Pre-pubertal stage:
– Growth is retarded in the absence of thyroid hormones.
– Hypothyroidism during this stage results in a form of
dwarfism.
• Thyroid hormone appears to be permissive or act
synergistically for normal growth of bones.

• Thyroid hormone is required for normal synthesis

and secretion of growth hormone.
– At puberty, increased androgen secretion drives an
increased growth hormone secretion.
– This will not occur with depressed levels of thyroid
hormones.
 Physiologic Actions Of Thyroid
Hormones: Metabolic
• Carbohydrate Metabolism:
– Stimulation of Carbohydrate Metabolism.
– Rapid uptake of glucose by the cells
– Enhanced glycolysis
– Enhanced gluconeogenesis
– Increased rate of absorption from the
gastrointestinal tract
 Physiologic Actions Of Thyroid
Hormones: Metabolic
• Stimulation of Fat Metabolism.
– lipids are mobilized rapidly from the fat tissue,
which decreases the fat stores of the body
– Increased thyroid hormone decreases the
concentrations of cholesterol, phospholipids,
and triglycerides in the plasma
– decreased thyroid secretion greatly increases
the plasma concentrations of cholesterol,
phospholipids, and triglycerides.
 Physiologic Actions Of Thyroid
Hormones: Metabolic
• Thyroid hormones are required for
conversion of carotene to vitamin A, and,
as a consequence, hypothyroid individuals
can suffer from Night blindness and
yellowing of the skin ( carotene gives
yellow color to skin).
 Effect on Protein Metabolism
• T4 in physiological doses: Anabolic (only
when secretion of GH is normal)
• T4 in high doses: Catabolic due to in BMR
• +++muscle weakness with undue
fatiguability(Thyrotoxic Myopathy)
• Mobilization of bone protein bone
mass(osteoporosis) hypercalcemia and
hypercalciurea
• Hypothyroidism catabolism variety
of proteins deposition under the skin and s/c
tissues exert osmotic pressure retention
of fluid & electrolytes dry,coarse and
puffy skin(called Myxoedema) it is non
pitting oedema commonly seen around the
eyes,hands,supra para ocular fossa.
Hypothyroidism
 Thyroid hormones:
Effects on Various Systems:
 Thyroid hormones:
Effects on Various Systems:
• Cardiovascular System
– Increased Blood Flow and Cardiac Output.
– Increased Heart Strength.
– Increased Heart Rate.
• Increased Respiration.
• Increased Gastrointestinal Motility.
 Thyroid hormones:
Effects on Various Systems:
• Excitatory Effects on the Central
Nervous System.
• Autonomic Nervous System:
– Increases the number and affinity of
adrenergic receptors, thereby increasing the
sensitivity to catecholamine
• Increased heart rate
• Tremor
 Thyroid hormones:
Effects on Various Systems:
• Muscular system:
– Excess thyroid hormone causes muscles weak
because of excess protein catabolism.
• Sexual Function:
– Needed for normal sexual maturation
– In women:
• Disturbances in Menstrual cycle
 . Effect on Sexual Function
i. lack of thyroid hormone cause Menorrhagia
(excessive menstrual bleeding ) and
Polymenorrhea (frequent menstrual bleeding)
greatly decreased Libido

ii. Hyperthyroid woman – Oligomenorrhea

(greatly reduced bleeding and Amenorrhea
(absence)

iii. In men – lack of thyroid hormone

causes loss of libido ; great excess cause impotence
 Physiologic Actions Of Thyroid
Hormones on different organ systems:
 Thyroid horomes:
Functions
• Growth and development:
– Brain during peri-natal period ( After birth)
– Acts synergistically with growth hormone for growth
during pre-pubertal period.
• Metabolic:
– Increased BMR
– Lipid metabolism
– Glucose absorption
• Different organ systems.
Thank You