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Capillary
(Rich blood
supply)
Basemen
t
membran
e
Cuboidal epithelial
cells
Physiology
The thyroid follicles secretes tri-iodothyronine(T3)and
thyroxin(T4)synthesis involves combination of
iodine with tyrosine group to form mono and diiodotyrosine which are coupled to form T3 andT4.
The hormones are stored in follicles bound to
thyrogobulin .
When hormones released in the blood they are
bound to plasma proteins and small amount
remain free in the plasma .
The metabolic effect of thyroid hormones are due to
free (unbound)T3 and T4.
90%of secreted hormones is T4 but T3is the active
hormone so, T4is converted to T3 peripherally.
Characteristics of Circulating T4
and
T
Hormone properties 3
T
T
4
8 g/dl
0.14
g/dl
0.02 %
0.3 %
21 X 10-12
M
6 X 10-12
M
7d
100 %
0.75 d
20 %
90 g/d
32 g/d
~ 20 %
~ 70 %
Functions
of
thyroid hormones
Abnormal
thyroid hormones
secretions
I: Hyperthyroidism
(thyrotoxicosis)
Hyperthyoidism THs.
Could be:
1ry hyperthyroidism (diseases is
in the gland), e.g. Graves disease
Exerts TSH-like effects on thyroid.
Not affected by negative
feedback.
T3 & T4 reflex TSH.
2ry hyperthyroidism (disease is
higher up)
TRH TSH T3 & T4.
I: Hyperthyroidism Graves
disease
Graves Disease
Diagnosis:
Low TSH, High FT4 and/or FT3
If eye signs are present, the diagnosis of Graves
disease can be made without further tests
If eye signs are absent and the patient is
hyperthyroid with or without a goitre, a radioiodine
uptake test should be done.
Radioiodine uptake and scan:
Scan shows diffuse uptake
Uptake is increased
TSH-R Ab (stim) is specific for Graves disease. May
be a useful diagnostic test in the apathetic
hyperthyroid patient or in the pt who presents with
unilateral exopthalmos without obvious signs or
laboratory manifestations of Graves disease
II: Hypothyroidism
Adult (Myxedema)
Hypothalamu
s
TR
H
Anterio
r
pituitar
TSH y +
NO or low
feedback
inhibition
Lack of
iodine
Thyroi
d
gland
Poo
r
Low T3 or T4
release
+++
Growth of
the gland
If there is absence of
deionization enzyme
NO recycle synthesis of DIT & MIT
accumulate.
Symptoms of Hypothyroidism:
- Decreased metabolic rate.
- Slow heart rate & pulse.
- Slow muscle contractions
- appetite, weight gain, &
constipation.
- Prolonged sleep, & dizziness.
- Coarse skin.
- Slow thinking, lethargy, & mask face.
- Intolerence to cold ( ability to adapt
cold).
- Myxoedema swollen & puffy
appearance of body, due to deposition of
Hypothyroidism
Diagnosis:
A iFT4 and hTSH is diagnostic of primary hypothyroidism
Serum T3 levels are variable (maybe in normal range)
+ve test for thyroid autoantibodies (Tg Ab & TPO Ab) PLUS
an enlarged thyroid gland suggest Hashimotos thyroiditis
With pituitary myxedema FT4 will be i but serum TSH will
be inappropriately normal or low
TRH test may be done to differentiate pituitary from
hypothalamic disease. Absence of TSH response to TRH
indicates pituitary deficiency
MRI of brain is indicated if pituitary or hypothalamic
disease is suspected. Need to look for other pituitary
deficiencies.
If TSH is h & FT4 & FT3 are normal we call this condition
subclinical hypothyroidism
II: Hypothyroidism
Children (Cretinism)
Thyroid Nodule
Very common
30 60 years old ; 4.2% ( Palpation)
19 67% by ultrasound
Autopsy ; 50%
Thyroid Nodule 2
Thyroid nodule very common
Thyroid cancer very rare but
curable
AIM IS NOT MISS THYROID CANCER
Thyoid Nodule
Invesigations
TFTs
Ultra sound scan
Thyroglobulin and Calcitonin not
recommended ( US Guidelines)
Fine needle Aspration(FNA)
Hashimotos Thyroiditis
Symptoms & Signs:
Usually presents with goitre in a patient who is
euthyroid or has mild hypothyroidism
Sex distribution: four females to one male
The process is painless
Older patients may present with severe
hypothyroidism with only a small, firm atrophic
thyroid gland
Transient symptoms of thyrotoxicosis can occur
during periods of hashitoxicosis (spontaneously
resolving hyperthyroidism)
Hashimotos Thyroiditis
Lab:
Normal or low thyroid hormone
levels, and if low, TSH is elevated
High Tg Ab and/or TPO Ab titres
FNA bx reveals a large infiltration
of lymphocytes PLUS Hurthle cells
Complications:
Permanent hypothyroidism (occurs
in 10-15% of young pts)
Rarely, thyroid lymphoma
TSH
Thyroxine (T4) (free / total)
Ttriiodothyronine (T3) (free / total)
Thyroid Antibodies: Autoimmune
thyroid disease is detected by
circulating antibodies against TPO and
Tg.
Imaging
Thyroid Ultrasound scan
Thyroid Isotope Scan
Guidelines
The diagnosis of primary hypothyroism
requires the measurement of both TSH and
T4
Patients with type-1 diabetes should have a
check of thyroid function included in their
annual review. Patients with type-2 diabetes
should have their function checked at
diagnosis but routine annual thyroid function
testing is not recommended
Patients stabilised on long term thyroxine
treatment should have TSH checked annually
Guidelines
The thyroid status of hypothyroid patients
should be checked with TSH + T4 during each
trimester
Ideally the following sequence of TFT should be
performed in the hypothyroid women during
pregnancy
Before conception
At time of diagnosis of pregnancy
At antenatal booking
At least once in 2nd and 3rd trimester
Again after delivery at 2 4 weeks post partum
Newly diagnosed hypothyroid will need testing
every 4 6 weeks until stable
Thyroid Antibodies
Thyroid Peroxidase(thyroid microsomal)
100% in Hashimato thyroiditis
87% with graves disease
Thyroglobulin Antibody
76% of Graves Disease
Thyroid receptor antibody
Normally present in 12 18 % of
female population
Measure TSH
Elevate
d
Measure unbound T4
Normal
Pituitary disease
suspected
No
yes
Low
Mild
hypothyroidi
sm
TPO Ab
(+)
or
symptom
atic
Normal
TPO Ab
(-)
or no
sympto
ms
Primary
hypothyroidi
sm
TPO
Ab
(+)
TPO
Ab (-)
No
further
test
Measure
unbound
T4
Lo
Norm
w
al
No
Rule out other
further
causes of
test
hypothyroidism
Autoimmune
Rule out drug effects,
T4 treatment
hypothyroidism
sick euthyroid
syndrome, then
Annual follow T treatment
4
Evaluate anterior
up
RIAs
Sensitivity 1mu/L
Cross reaction < 1
%
Hypothyroid
Hyperthyroid
TSH 0.05 - 0.11mu/L
Detecti
on
ICMAs
< 0.1
Euthyroid
0.4 4.0
IRMAs
Sensitivity
10 - 200 x RIAs
Hypo +
euthyroid
Hypothyroid
4 m U/L
II
Immunoassay
I : 5 7 mU/L
II: 0.1 0.2
Immunoassay
III: 0.01 0.02
IV: 0.001 0.002
Anti TPO
105 kDa, microsomal
Thyroid peroxidase
enzyme
Pos correlation: anti TPO
& PPTD
Complement activation
AntiTSH-R
Hyperthyroid
Hypothyroid
!! In GD
Ab bispecific: Ab
(+) TPO more frequent & higher than anti
Only anti TPO (+): rare
Anti TPO & anti Tg in GD: not established (discussion)
Prevalence of anti
Ab
bispecific
TPO
PPTD: 16 %
N population: 1.4
thyroiditis): 16 %
Anti Tg
Iodium Deficiency
Detection AIT (Goiter +)
Monitoring jodium Tx
Tiroglobulin (Tg)
Precursor of thyroid H
Produced in thyroid gland
Secretion to colloid
T Hashimoto: 80 %
Thyroid H reserved
GD : 60 %
Thyroid carcinoma: 30 %
IHA < 1: 1000
Normal: 3-18 %
Anemia Perniciosa
Syogren Syndrome
traffic intracellular Tg
Early indicator of PPTD
Rise in GD
Target anti Tg
Serum Tg Examination
Not distinguished: PPTD & GD
Interference: serum anti Tg
(reaction of anti Tg + anti Tg
antibody in immunoassay kit),
examination simultaneously Tg
+ anti Tg