The thyroid gland

Gross anatomy and histology of the

thyroid gland
Thyroid hormone synthesis
Thyroid hormone secretion, peripheral
conversion and metabolism
Measurement of free T4 and TSH
Actions of thyroid hormones, hyper-
and hypothyroidism.
 20 grams

4 cm

Blood supply
Superior and inferior thyroid arteries from external
carotids and subclavian arteries respectively
Superior, middle and inferior thyroid veins
More blood per unit weight than kidney - goitre bruit
Histology of the
thyroid gland
Thyroid hormones derived from two iodinated
tyrosine molecules

 Synthesis of thyroid hormones
Active uptake of iodide into follicular cell
Iodide iodine - H2O 2 (catalysed by
TPO)
Active uptake of iodine at follicular/
colloid interface
Incorporation of iodine onto tyrosine
residues of thyroglobulin
Coupling of iodinated tyrosines
Storeage of T3 and T4
Active transport of iodine (ATPase dependent) against
electrical and chemical gradient - concentration of
iodine 30-50 times that of the circulation
 Active uptake of iodine
by a sodium iodide
symporter

Oxidation of iodide to
iodine

Iodination of tyrosine
residues at
apical/colloid interface
to form MIT and DIT
Uptake of
thyroglobulin into the
lumen of the follicle
Incorporation of iodine onto tyrosine residues
on the thyroglobulin molecule
4) Release of T4 and T3 into
circulation -

100g T4 & 10 g T3/day

3) ~ 10% T4 undergoes mono-

deiodination to T3 before secretion

2) Fusion of colloid droplets with

lysosomes --> hydrolysis and
release of thyroid hormones

1) Stimulated by TSH colloid

droplets with the bound thyroid
hormones are taken back into
follicular cells by pinocytosis
Daily production
of thyroid
hormone
secretion and
serum
concentrations
5
Thyroid hormone
5 metabolism

5 5

3 3
 Metabolism of thyroid hormones
Series of deiodinations by deiodinases
Type 1 - liver, kidney, thyroid, pituitary gland,
CNS: 5 and 5 positions
Type 2 - brain, brown fat, placenta, pituitary
gland: 5 position only: T4 T3 only:
intracellular concentrations of T3
Type 3 - brain, placenta: 5 position only
T4 T3
Other metabolic pathways: sulphation,
decarboxylation, conjugated with glucuronide
 Thyroxine (T4) other
pathways
1&2 1&3

T3 S
T3 3,5,3 rT3 3,5,3

T2 T2 Type 1 - 5 and 5
Type 2 - 5 only
T1 T1 Type 3 - 5 only

thyronine
 Control of thyroid
hormone synthesis
and release and
feedback control
 TSH Receptors
TSH
G protein linked receptor

cAMP IP3 + DAG

Protein Ca2+ Protein

Kinase A Kinase C
(high concentrations)
 Actions of TSH
Active uptake of iodine*
Stimulates other
reactions involved in
thyroid hormone
synthesis
Stimulates the uptake of
colloid
Induces growth of the
thyroid gland
Thyroid hormone receptors
 Thyroid hormone receptors
Type 2 receptors in nucleus - high affinity
for T3
Dimerize with another T3 receptor
(homodimer) or retinoic acid receptor
(heterodimer)
Dimerized receptor + other transcription
factors gene transcription
Membrane receptors? Ion movements
Isoforms of the thyroid hormone receptor

DBD

DBD

DBD

DBD
Dimerization of thyroid hormone receptors and
gene activation/inactivation
T3
Functions of thyroid hormones
Stimulate metabolic rate: increasing number and
size of mitochondria, increasing enzymes in the
metabolic chain, increasing Na+/K+ ATPase activity.
Resting metabolic rate may increase 100% with
excess thyroid hormones or decrease by 50% with a
deficiency
Positive inotropic and chronotropic effects on
the heart
Important in growth and development -
particularly skeleton and nervous system
 Feedback
control of
thyroid
hormone
synthesis and
secretion
 Radioisotopic (technetium) scanning of the
thyroid gland - regional function of the gland

No left lobe hyperthyroidism

hypothyroidism

Hot nodule
Cold nodule
 Measuring free T4
Phosphate
1) Add serum sample or
standard (T4 ) to latex
beads coated with Abs

2) Add T4 labelled with

alkaline phosphatase.
This will bind to any
unoccupied Ab binding
sites

3) Add a substrate that

will fluoresce when the
alkaline phosphatase
removes a phosphate
group

4) Fluorescent intensity
will be inversely
proportional to the
concentration of T4
Assay of antibodies to the human TSH
receptors
Patients serum Add Precipitate Count
+ TSH 125I-TSH
receptors (bovine)
(porcine)
 Circulating concentrations of TSH and pituitary
function test in normal and primary hyperthyroidism
 Saggital MR scans of a) normal and b) a patient with a
craniopharyngioma causing bitemporal hemianopia and
hypopituitarism
Primary hyperthyroidism Hypothyroidism
 Graves disease (10)

Autoimmune - activating ABs to TSH

receptor
High concentrations of circulating
thyroid hormones, low TSH
Weight loss, tachycardia, tiredness
Diffuse goitre - TSH stimulating
growth
Opthalmompathy and dermopathy
Symptoms and signs of hyperthyroidism
 Hashimotos (1o)

Autoimmune - ABs destruction of

thyroid gland
Low concentrations of thyroid hormones,
high TSH
Lethargy, intolerance to cold
Lack of growth and development
Diffuse goitre - lymphocytic infiltration
of gland + TSH stimulated growth
Symptoms and signs of hypothyroidism