LMP299Y1 Lecture Notes - Lecture 8: Congenital Hypothyroidism, Thyroid, Thyrotropin Receptor

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Published on 12 Apr 2013
School
UTSG
Department
Laboratory Medicine and Pathobiology
Course
LMP299Y1
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LECTURE EIGHT: THYROID DISEASES
GOITER
It can be associated with both hyperthyroidism and hypothyroidism
The patient may also have normal thyroid function
THYROID GLAND AND THYROID HORMONES
Thyroid gland secreted mostly T4 and some T3. The peripheral tissues (e.g. the liver and kidney) deiodinate
(convert) T4 to produce 2/3 of the circulating T3
Thyroid hormones bind to receptors and trigger the hormonal effects. T3 is more biologically active than T4, but
at a lower concentration in plasma (2 nmol/L for T3 vs 100 nmol/L for T4)
Reverse T3 (rT3) is an inactive form metabolized from T4. Local thyroid status can be modulated by the relative
production of T3 and rT3.
Thyroid hormones are essential for the normal maturation and metabolism of all the tissues in the body.
Reverse T3 and is the inactive form this is how the peripheral issue can fine tune the levels of T3 in the body
TOTAL VS. FREE
Reversibly bound to carrier proteins
e.g. T4-binding globulin (TBG)
Only very small fraction is unbound and free for biological activity
Total nmol/L Free pmol/L
Free T4 0.03% of total T4
Free T3 0.3% of total T3
Alterations in the concentration or affinity of binding proteins may change the concentration of thyroid
hormones (i.e. we can modify the levels of the thyroid hormones using the levels of the binding proteins)
This is how they are
synthesized they
start with the
tyrosine and then
there are a couple
of the iodonization
reactions
It is called T4 since there are 4
iodines on the molecule
Can get rid of one of the
iodines and form T3
- get rid of a
DIFFERENT iodine and
we get this form
- remember that rT3 is
made by the tissues
Question: FT4 and FT3 vs. total T4 and total T3, which are the better markers in routine assessment of thyroid
function (Why?) (we use the free levels of the T3 and the T4 since the total is changed by the levels of the
binding proteins THE FREE IS NOT AFFECTED BY THE LEVELS OF BINDING PROTEINS)
CHANGES OF TBG BINDING AFFECTS THYROID FUNCTION TESTS
CAUSE
COMPOUND
EFFECTS
Increase TBG
- Estrogen
- Oral Contraceptive
T4, T3 (the total T4 and T3 will
be increased) / FT4, TSH
(the free TSH and free T4 will stay
normal)
Decrease TBG (there is decreased
concentration of the thyroid binding
globulin)
- Androgen
- Glucocorticoids
T4, T3 (there is less of it being
bound hence the total levels of the
T4 and T3 decrease) / FT4,
TSH (does not change it is the free
T4 and TSH)
Inhibit binding of T4/T3 to TBG
(This medication can compete for the binding
of thyroid hormones to their binding globulins
the free T4 will be maintained while the
bound T4 will be decreased (and hence total
t4) is decreased)
- Salicylates
T4 / FT4
MYXEDEMA (this is a symptom of severe hypothyroidism)
Dry, waxy swelling of the skin, with abnormal deposits of glycosaminoglycan’s (unbranched polysaccharides)
(there is a gradual changes in the facial features)
SYMPTOMS AND SIGNS OF HYPOTHYROIDISM HYPOMETABOLIC SYNDROME
SYMPTOMS:
- Weight gain - Growth retardation in children (the child is not growing as fast as the peers
are)
- Depression - Deep, hoarse voice
- Easy fatigue - Dry, coarse skin
- Lethargy (feel tired) - Cold intolerance
- Myxedema (dry skin) - Hair loss
- High Cholesterol (there is decreased synthesis of the LDH receptor)
- Constipation
- Bradycardia (slow heart rate)
These symptoms are not specific for hypothyroidism e.g. people that have anemia or diabetes can also have
fatigue (lethargy), and weight gain and depression
CAUSES OF HYPOTHYROIDISM
1. Primary Hypothyroidism (this is the most common)
- Autoimmune destruction of the thyroid gland (it gradually loses its function) (Hashimoto’s disease)
- Radioiodine or surgical treatment of hyperthyroidism (this may cause it)
- Iodine deficiency (in certain regions of the world such as in central Africa this is common cause of the
hypothyroidism (not enough iodine to make T3 and T4)
- Congenital defects in hormone biosynthesis and action
- Transient hypothyroidism due to drug therapy (anti-thyroid drugs) (may revert to normal if the drug is
stopped; they are initially give a drug to reduce their HYPERthyroidism BUT it is too effective and hence
leads to hypothyroidism if the drug is stopped the they may revert to normal (transient))
2. Secondary Hypothyroidism
- Pituitary disease
3. Tertiary Hypothyroidism
- Hypothalamic disease (cannot produce TRH)
DIAGNOSTIC STRATEGY FOR SUSPECTED HYPOTHYROIDISM (this is how we diagnose it)
COMPLICATIONS OF HYPOTHYROIDISM
Depending on when during life a patient is hypothyroid, clinical outcomes vary.
Pregnancy: irreversible fetal malformation, growth retardation and neurological deficits (this is permanent
even after birth)
Infancy & early childhood: decreased linear growth, inadequate brain maturation, low IQ and psychomotor
development; severe condition (this is treatable if its discovered early enough) Cretinism
Adult: severe condition death from myxedema coma
- Longstanding severe hypothyroidism facing a precipitating factor, e.g. infection, a cardiovascular event,
sedating medication
- Features: severe hypothermia (<80°F) and loss of consciousness
NOTE: Demonstrate the importance of thyroid hormones
CRETINISM (They cannot produce the thyroid hormone other causes are the pituitary hormone)
Congenital Hypothyroidism
o Occurs with a frequency of one in 4,000 live births
o May be due to absence of the thyroid gland or may occur secondarily to defects of thyroid hormone synthesis
o Delays in treatment results
o CRETINISM: mental retardation, short stature, deaf, neurological signs, etc.
o If diagnosed at an early age, replacement thyroid hormone (thyroxine supplement allows them for early life)
can be given and normal development can occur
TSH is the normal hormone that stimulates the
thyroid gland and it there is low TSH then the
feedback should increase the levels of the TSH.
This is the specific thyroid test
Excludes the possibility
of the hypothyroidism-
they are fine from this
point of view
diagnosed with the
true version yet we
need to monitor them
and they may
This is due to the destruction or
the loss of the function of the
thyroid gland it is called primary
since it is in the thyroid gland itself
(secondary is one level up (this
would be the pituitary)
The thyroid gland is not making the T4
This is due to the
pituitary disease. This is
due to the pituitary not
making the TSH and
hence there is no release
of the T4

Document Summary

It can be associated with both hyperthyroidism and hypothyroidism. The patient may also have normal thyroid function. Thyroid gland secreted mostly t4 and some t3. The peripheral tissues (e. g. the liver and kidney) deiodinate (convert) t4 to produce 2/3 of the circulating t3. Thyroid hormones bind to receptors and trigger the hormonal effects. T3 is more biologically active than t4, but at a lower concentration in plasma (2 nmol/l for t3 vs 100 nmol/l for t4) Reverse t3 (rt3) is an inactive form metabolized from t4. Local thyroid status can be modulated by the relative production of t3 and rt3. Thyroid hormones are essential for the normal maturation and metabolism of all the tissues in the body. Reverse t3 and is the inactive form this is how the peripheral issue can fine tune the levels of t3 in the body.