Hypothyr oidis

m
By

Dr Ehsan Wafa
 T he T hyroid Gland

 Butterfly-shaped
endocrine organ
consisting of two lobes on
either side of the trachea
connected by an isthmus
located just below the
larynx in the front of the
neck.
 T hyr oid Gland

Largest endocrine gland.

Develop as a bud from floor of pharynx .
Descend to it’s level in the neck
• Thyroid follicle or acinus is the functional unit of the gland
•Thyroid follicles are lined by epithelial cells & full of colloid.
• Thyroid cells synthesize thyroid hormones that are stored in the
colloid.
 T he T hyroid Hor mones

The thyroid
hormones T4 &T3
are essential for :
 Normal growth
and development,
 Regulation of
metabolic rates in
every cell of the
body.
 Regulation of Thyroid
Hormone Synthesis & Release
•Hypothalamus → thyrotropin
releasing hormone (TRH),
which stimulates the anterior
pituitary to secrete thyroid-
stimulating hormone (TSH).

•TSH binds to receptors on

epithelial cells in the thyroid
gland, stimulating synthesis
and secretion of thyroid
hormones.
The thyroid hormones are basically two tyrosines linked
together with the critical addition of iodine at three or four
positions on the aromatic rings.
Biosynthesis of Plasma iodide
thyroid hormones
1 Iodine Trapping
iodide
Oxidation to active
Organification

iodine
2 Iodine

Iodination of tyrosine Mono & Di-iodotyrosine

MIT + DIT
3 Coupling
Tri & Tetra -iodothyronine
4 Storage & release T3 & T4
T4 &T3
 Release of stored
thyroid hormones
1. Endocytosis of
thyroglobulin
2. Fusion of endosome with
lysosome.
3. Proteolysis of
thyroglobulin.
4. Diffusion of free thyroid
hormones into the blood.
 Physiological effects
 Icrease BMR
 Bone growth
 Maturation of brain neurons
 CHO: potentiate insulin action in physiological amounts while
hyperglycemic in pharmacological amounts

 Protein: anabolic in physiological amounts while catabolic in

pharmacological amounts

 Lipid: increase all aspects of metabolism including synthesis,

mobilization ,and utilization
 What is secreted?
What is active?
 A large majority of the thyroid hormone secreted from the
thyroid gland is T4, but T3 is the considerably more active
hormone.

 Although some T3 is also secreted, the bulk of the T3 is

derived by deiodination of T4 in peripheral tissues,
especially liver and kidney. Deiodination of T4 also yields
reverse T3, a molecule with no known metabolic activity.
 Cr etinism
Mentally retarded dwarf

 Mentally retardation.
 Short stature with
infantile proportions.
Endemic Goiterous
Hypothyroidism due to

iodine deficiency
 Congenital
Hypothyroidism
Cretinism
 Shor t with infantile
pr opor tions.

 Developmental delay
( Mental deficiency).

 Char acteristic
featur es.
 Congenital
Hypothyroidism
Cretinism
 Coarse facial features.
 Head disproportionately large.
 Delayed closure of fontanels.
 Low anterior hair line.
 Hair dry & brittle.
 Congenital
Hypothyroidism
Cretinism
 Puffy eyes
 Hypertelorism
 Flat base of the nose
 Infantile nasolabial configuration
 Large protruded tongue
 Short neck with
redundant folds.
 Neonatal Hypothyroidism
Early Diagnosis?
 Mostly ASYMPTOMATIC !!

Affected infants often appear normal at birth.

 If Symptomatic, mostly nonspecific.

 Neonatal screen is essential.

 High index of suspicion. ( early signs) ?
 Early Signs of Congenital
Hypothyroidism
in the newborn
 Hypothermia.  Large at birth.
 Sluggish & sleepy.  Wide fontanels.
 Feeding difficulty.  Posterior fontanel >0.5 cm.
 Respiratory difficulty.  Umbilical hernia.
 Mottling of the skin & cold  Large tongue.
extremities.
 Goiter may be present.
 Constipation.
 Prolonged physiologic
 Hypotonia. jaundice.
 Hypothyroidism

Non-goitrous Goitrous
 Congenital Non-goitrous
Hypothyroidism
 95% Developmental  5% Other causes :
defect : – TRH deficiency.

– Hypoplasia. – TSH deficiency.

– Aplasia or athyrosis. – TSH

unresponsiveness.
– Ectopia ( often
hypoplastic) – Anti-thyroid immunity
 Congenital Goitrous
Hypothyroidism
 Dyshormonogenesis  Iodine deficiency (endemic
goitrous hypothyroidism)
– Trapping defect.
– Organification defect.  Maternal goitrogenic
drugs :
– Coupling defect.
–Iodides.
– Deiodination defect.
–Amiodarone.
– Thyroglobulinn –Antithyroid drugs.
synthesis defect.
 Scr eening for
Congenital
Hypothyr oidism
Why ?
 Commonest cause of Preventable Mental Retardation.

 Treatment has to be early to obtain normal mental & physical

development.

 Affected infants often appear normal at birth.

 Signs & symptoms in the newborn & young infant are often
minimal & non specific. Classic S&S appear gradually over 3-6m.

 Only 5-10 % of cases can be diagnosed in the first month without

screening.

 Missed cases will be Mentally retarded dwarfs.

 Missed cases of congenital
Mentally Retarded hypothyroidism from Egypt
Dwarf
• Short with infantile proportions. . Large tongue
• Hoarse cry.
• Umbilical hernia.
• Mental deficiency if not treated early.
Reversal of physical stigmata of cong. Hypothyroidism
by treatment.
Scr eening for Congenital
Hypothyr oidism

 Best chance for normal or near normal intellectual

development.

 6-12 % false negative due to laboratory errors.

 Physicians should continue looking for signs & symptoms

suggestive of congenital hypothyroidism.
 Scr eening for
Congenital
Hypothyroidism
How ?
 All newborns.
 3rd -7th day after birth.
 Blood specimens by heel stick.
 Adsorbed onto filter paper.
 Air dried.
 Analyzed in central lab. For TSH.
 Abnormal results reported to parents & treatment centre.

---------------------------------------------------------------------
Some countries use T4 screen.
 Treatment of congenital
hypothyroidism : Objectives
To ensure normal growth and development.
To maintain the serum total T4 in the upper half of
the normal range (10 to 16 ug/dl, with a serum
TSH suppressed into the normal range (usually
below 10 mU/L).
 Treatment of congenital

What to give, How

 L thyroxin tablets, No liquid formulation.
much ?
 Initial dose :
in the newborn & young infants: 10-15ug/kg/day.
Infants 6-12 months: 6-8ug/kg/day.
1-5 yrs 5ug/kg/day.
Older children 4ug/kg/day.
Adults 2ug/kg/day.
 Monitor response clinically & Labs : T4 & TSH
 Adjust dose to maintain the serum total T4 in the upper half of the
normal range (10 to 16 ug/dl, with a serum TSH suppressed into the
normal range (usually below 5 mU/L).
 Treatment of congenital

How ?
Use only L thyroxin tablets.
Thyroxine tablets can be crushed daily, mixed
with a few ml of water, breast milk, or formula,
and fed to the infant.

Do not give it with iron, soy protein formula, as

they bind T4 & inhibit absorption.
 Treatment of congenital

For how long ?

Most cases are permanent hypothyroidism &
require treatment for life.

Some case are transient

Delay any test for permanency to after 3 years
 Follow up of congenital
hypothyroidism
 Periodic follow up of growth & development.
 Follow up of total T4 & TSH :
At 2 and 4 weeks after the initiation of L-thyroxine treatment

Every 1 month during the first year of life

Every 2 months between 1 and 3 years of age

Every 3 months thereafter until growth is completed

At more frequent intervals when compliance is questioned or

abnormal values are obtained
 ASSESSMENT OF PERMANENCE
OF HYPOTHYROIDISM
Permanent hypothyroidism can be assumed :
 If the thyroid uptake and/or scan reveals an ectopic
gland or absent thyroid tissue.
 If the serum TSH is seen to increase above 20 mu/l
after the first year of life, presumably because of
insufficient T4 replacement
 ASSESSMENT OF PERMANENCE
OF HYPOTHYROIDISM
When permanence of thyroid disease is not
established :
 L-thyroxin administration should be
discontinued for 30 days, at some point after
the child is 3 years of age. At that time,
 Serum should be obtained for measurement
of T4 and TSH levels. If the T4 is low and the
TSH level is elevated, permanent
hypothyroidism is confirmed and therapy is
reinstituted.
Questions &

Problems
 Congenital hypothyroidism can present in
the neonatal period by all the following
EXCEPT ONE:

 a) Hypothermia.
 b) Lethargy and poor feeding.
 c) Prolonged physiologic jaundice
 d) microglossia.
 Increased TSH Can be due to:

 a) Low T4.
 b) Low thyroxin binding globulin.
 c) High T4 or T3
 d) Exogenous L thyroxin.
Adequate treatment of hypothyroidism

Choose correct answer

 a) Low T4 & high TSH
 b) T4 upper normal value for age & low but
detectable TSH

 c) High T4 & undetectable TSH

 d) High T3/T4 ratio.
 Neonatal screening for hypothyroidism in
EGYPT is done on

 a) Days 1-3
 b) Days 3-7.
 c) from cord blood.
 d) Any time in the first month.
 Case 1
 A full-term infant had prolonged jaundice,
poor feeding, constipation and lethargy
during the neonatal period.

 He is not seen again until 6 months of age

when coarsening of the face, flattened
nasal bridge, enlarged tongue, and
hoarse cry are noted.
 Case
Of the following, the MOST likely Diagnosis is :

A. Down’s Syndrome
B. Congenital hypothyroidism.
C. Neonatal jaundice.
D. TORCH Infection
E. Post-kernicterus
 Case
Of the following, the likely Associated findings
are :

A. Short stature.
B. Delayed bone age.
C. Developmental delay.
D. Cold extremities
E. Umbilical hernia.
 Short.
 Large tongue.
 Coarse features.
 Umbilical hernia.
 Hoarse cry.
 Case
Of the following, the MOST likely cause of
hypothyroidism in an infant is :

A. Agenesis of the thyroid gland

B. Endemic goitrous hypothyroidism
C. End-organ unresponsiveness to thyroid hormone
D. Inborn error of thyroxin synthesis
E. Thyroid gland unresponsiveness to thyrotropin
 Case
Which of the following, GOITER can be found :

A. Agenesis of the thyroid gland

B. Endemic goitrous hypothyroidism
C. Thyrotropin deficiency.
D. Inborn error of thyroxin synthesis
E. Maternal drugs containing iodides.