Thyroid and its Functions

Dr Raghuveer Choudhary
HUMAN STRUCTURE - FUNCTION
ENDOCRINOLOGY
THYROID
Thyroid follicles serve as
both factory and
warehouse for thyroid
hormones.
 Formation and Secretion of the Thyroid
Hormones

 Accumulation of the raw materials

 Synthesis of the hormones and storage

 Release of the free hormones and secretion

into blood
Two Principle Raw Materials

 Tyrosine is provided from a large glycoprotein

called thyroglobulin, which is synthesized by
thyroid epithelial cells and secreted into the lumen
of the follicle .
 Iodine, or more accurately iodide (I-), is avidly
taken up from blood by thyroid epithelial cells,
which have “iodide pumps” on their membrane.
 Iodide Metabolism
 daily requirement of iodine ~ 100-200 µg
 Daily average intake of iodine- 500 µg
 ~minimum requirement to prevent goiter-75 µg/day
 Neonatal iodine requirement is 40 µg/day
 During pregnancy iodine requirement ~ 200 µg/day
 Normal plasma iodide level is 0.15-0.3 µg%
 Thyroid gland contains 5-8 mg of iodide(95% of total
iodide content of body)
 Iodide Metabolism
 minimum daily requirement ~ 100-150 µg
 thyroid secretes ~ 80 µg per day as T3/T4
 ~ 60 µg is metabolised in the liver
 subsequent release of I- into the ECF
 total I- added to the plasma/day ~ 600 µg
 500 µg - average "Western" dietary intake
 60 µg - from the liver metabolism of T3 & T4
 40 µg - diffusion from the thyroid to the ECF
Iodide Trapping
 thyroid concentrates I- by actively transporting it
from the plasma into the colloid, the mechanism
for which is termed iodide trapping
 thyroid cells have a resting Em ~ -50 mV
 I- is transported against this electrical gradient by
an active basal pump
 once intracellular, it then diffuses down its dEC
gradient into the colloid
Iodide Trapping
 active transport is stimulated by TSH
 dependent upon the Na+/K+-ATP'ase
  inhibited by ouabain
 other glands which transport I- against a dEC gradient
include,
 salivary glands & gastric mucosa
 placenta
 ciliary body of the eye
 choroid plexus
 mammary glands
 NB: these are insensitive to TSH and their role is uncertain
various monovalent ions compete with iodide for uptake
  T/S ratio to ~ 1.0,
(normal T/S ratio-25-50:1)
chlorate & perchlorate
pertechnetate
periodate & bi-iodate
nitrate
 Thyroid Hormones
 principal hormones secreted by the thyroid are,
 Thyroxine T4
 Tri-iodothyronine T3
 the later also produced in the peripheral tissues by
deiodination of T4 (~ 80% of T3)
 both hormones are iodine containing amino-acids
 T3 is more active than T4
 reverse T3 (rT3) is inactive
 naturally occurring forms are the l-isomers
Thyroid Hormones
Synthesis of Thyroid Hormone
 Thyroid Hormone Synthesis
 Iodide Transport:
 An active transport
mechanism (pump) on
the basal surface of the
thyroid follicle cell.
 Thyroid Hormone Synthesis
 Oxidation of I- to I°
 The enzyme, peroxidase,
which is located at the
apical border of the follicle
cell, catalyzes oxidation of
I- to Io
 Peroxidase also catalyzes
iodination and coupling.
 Thyroid Hormone Synthesis
 Thyroglobulin
Synthesis: .
 Thyroglobulin: A high
molecular weight
protein is synthesized
in follicular
epithelium.
 Thyroid Hormone Synthesis
 Iodination
 As thyroglobulin is
extruded into the follicular
lumen, a portion (<20%) of
its tyrosine residues are
iodinated. The catalyst for
this reaction is peroxidase.
 The initial products of
iodination are:
 Mono- and di-iodotyrosine
(MIT and DIT)
Thyroid Hormone Synthesis
 Coupling:
 Peroxidase also
promotes the coupling
of iodinated tyrosine in
the thyroglobulin
molecule.
Synthesis of Thyroid Hormones
Thyroid Hormone Synthesis
Coupling:
 When two DITs couple, Tetra-iodothyronine
(T4) is formed.
 When one DIT and one MIT combine, tri-
iodothyronine (T3) is formed.
 When iodine is abundant mainly T4 is formed.
But when iodine becomes scarce the production
of T3 increases.
Thyroid Hormone Synthesis
 Storage of Thyroid
Hormones:
 Enough hormone is
stored as iodinated
thyroglobulinin the
follicular colloid to last
the body for 2-3
months.
Synthesis of Thyroid Hormone
Thyroid Hormone Synthesis
SECRETION OF THYROID
HORMONE
 Endocytosis: - Pieces of the follicular colloid are
taken back into the follicle by endocytosis.
 Fusion-The endocytosed material fuses with
lysosomes, which transport it toward the basal
surface of the cell.
 Proteolysis of thyroglobulin: Within the
lysosomes, the thyroglobulin is broken into free
amino acids, some of which are T4,T3, DIT, and
MIT.
SECRETION OF THYROID
HORMONE
SECRETION OF THYROID
HORMONE
 Secretion-T4 and T3 are secreted into the blood
 Normal condition: T4>>T3
 Iodine deficiency: T3>>T4
 Deiodination-A microsomal deiodinase removes
the iodine from iodinated tyrosines (DIT and MIT)
but not from the iodinated thyronines (T3 and T4).
 The iodine is then available for re-synthesis of
hormone. (Individuals with a deficiency of this
enzyme are more likely to develop symptoms of
iodine deficiency.)
Percentage Distribution
 TRANSPORT OF THYROID
HORMONES IN BLOOD

 Equilibrium between
Bound and Free
Circulating Thyroid
Hormone
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.
Activation And Degradation Of Thyroid
Hormone
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
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