Sumant Sharma MD CIC.

Regional Lab Nejran. KKSA

 Neonatal screening reveals incidence that
varies between 1-5/1000 live births
 The most common cause of preventable
mental retardation in children
 Both acquired & congenital forms are
linked to iodine deficiency
 Diagnosis is easy & early treatment is
beneficial
 CONGENITAL
Hypoplasia & mal-descent
Familial enzyme defects
Iodine deficiency (endemic cretinism)
Intake of goitrogens during pregnancy
Pituitary defects
Idiopathic
 ACQUIRED
Iodine deficiency
Auto-immune thyroiditis
Thyroidectomy or RAI therapy
TSH or TRH deficiency
Medications (iodide & Cobalt)
Idiopathic
 Grade 0: Not visible neck extended &
Not palpable
 Grade 1: Not visible, but palpable
 Grade 2: Visible only when neck is
extended & on swallowing,
 Grade 3: Visible in all positions
 Grade 4: Large goiter
 Derived from pharyngeal endoderm at
4/40
 Migrate from base of the tongue to cover
the 2&3 tracheal rings.
 Blood supply from ext. carotid &
subclavian and blood flow is twice renal
blood flow/g tissue.
 Starts producing thyroxin at 14/40.
 Maternal & fetal glands are independent
with little transplacental transfer of T4.
 TSH doesn’t cross the placenta.
 Fetal brain converts T4 to T3 efficiently.
 Average intake of iodine is 500 mg/day.
70% of this is trapped by the gland against
a concentration gradient up to 600:1
 Iodine & tyrosine form both T3 & T4 under
TSH stimulation. However, 10% of T4
production is autonomous and is present in
patients with central hypothyroidism.
 When released into circulation T4 binds to:
Globulin TBG 75%
Prealbumin TBPA 20%
Albumin TBA 5%
 Less than 1% of T4 & T3 is free in plasma.
 T4 is deiodinated in the tissues to either
T3 (active) or reverse T3 (inactive).
 At birth T4 level approximates maternal
level but increases rapidly during the first
week of life.
 High TSH in the first 5 days of life can give
false positive neonatal screening
 Is a Glico-protein with Molecular Wt of
28000
 Secreted by the anterior pituitary under
influence of TRH
 It stimulates iodine trapping, oxidation,
organification, coupling and proteolysis of
T4 & T3
 It also has trophic effect on thyroid gland
 T4 & T3 are feed-back regulators of TSH
 TSH is stimulated by a-adrenergic
agonists
 TSH secretion is inhibited by:
Dopamine
Bromocreptine
Somatostatin
Corticosteroids
 Conversion of T4 to T3 is decreased by:
Acute & chronic illnesses
b-adrenergic receptor blockers
Starvation & severe PEM
Corticosteroids
Propylthiouracil
High iodine intake (Wolff-Chaikoff effect)
 Total T4 level is decreased in:
Premature infants
Hypopituitarism
Nephrotic syndrome
Liver cirrhosis
PEM
Protein losing entropathy
 Total T4 is decreased when the
following drugs are used:
Steroids
Phenytoin
Salicylates
Sulfonamides
Testosterone
Maternal TBII
 Total T4 is increased with:
 Acute thyroiditis
 Acute hepatitis
 Estrogen therapy
 Clofibrate
 iodides
 Pregnancy
 Maternal TSI
 Thyroid hormones are essential for:
Linear growth & pubertal development
Normal brain development & function
Energy production
Calcium mobilization from bone
Increasing sensitivity of b-adrenergic
receptors to catecholeamines
Sumant Sharma. MD CIC
Classification of Hypothyroidism
Primary hypothyroidism(90%) is characterized by a high serum
thyrotropin (TSH) concentration and a low serum free thyroxine (T4)
concentration.
Subclinical hypothyroidism is defined biochemically as a normal free
T4 concentration in the presence of an elevated TSH concentration. Other
terms for this condition are mild hypothyroidism, early thyroid failure,
preclinical hypothyroidism, and decreased thyroid reserve.
Secondary (central) hypothyroidism is characterized by a low serum
T4 concentration and a serum TSH concentration that is not appropriately
elevated.
Transient or temporary hypothyroidism can be observed as a phase of
subacute thyroiditis.
Consumptive hypothyroidism, identified in an increasing number of
clinical settings, is the result of accelerated inactivation of thyroid
hormone by the type 3 iodothyronine deiodinase (D3).
 Gestational age > 42 weeks
 Birth weight > 4 kg
 Open posterior fontanel
 Nasal stuffiness & discharge
 Macroglossia
 Constipation & abdominal distension
 Feeding problems & vomiting
 Non pitting edema of lower limbs & feet
 Coarse features
 Umbilical hernia
 Hoarseness of voice
 Anemia
 Decreased physical activity
 Prolonged (>2/52) neonatal jaundice
 Dry, pale & mottled skin
 Low hair line & dry, scanty hair
 Hypothermia & peripheral cyanosis
 Hypercarotenemia
 Growth failure
 Retarded bone age
 Stumpy fingers & broad hands
 Skeletal abnormalities:
Infantile proportions
Hip & knee flexion
Exaggerated lumbar lordosis
Delayed teeth eruption
Under developed mandible
Delayed closure of anterior fontanel
 Overt obesity
 Myopathy & rheumatic pains
 Speech disorder
 Impaired night vision
 Sleep apnea (central & obstructive)
 Anasarca
 Achlorhydria & low intrinsic factor
 Decreased bone turnover
 Decreased VIII, IX & platelets adhesion
 Decreased GFR & hyponatremia
 Hypertension
 Increased levels of CK, LDH & AST
 Abnormal EEG & high CSF protein
 Psychiatric manifestations
Insideous onset fatigue ,lathargy
Cold Intolerance
Decreased Memory, Concentration
Constipation, Hearing Imairement
Muscle Cramps Arthralgias.
Weight gain
Menorrhagia
Depression
Carpel Tunnel Syndrome.
 Dry Coarse skin
 Dull facial expression
 Periorbital Puffiness
 Nonpitting swollen hands,feet.
 Bradycardia,Hypothermia
 Macroglossia,Goitre especially in Hashimoto’s
patients.
 Impalpable Thyroid if totally atrophied Thyroid.
 Autoimmune diseases (Diabetes Mellitus)
 Cardiomyopathy & CHD
 Galactorrhoea
 Muscular dystrophy + pseudohypertrophy
(Kocher-Debre-Semelaigne)
 DRUGS
Anti-thyroid
Cough medicines
Sulfonamides
Lithium
Phenylbutazone
PAS
Oral hypoglycemic agents
 FOOD
Soybeans
Millet
Cassava
Cabbage
 Neurological manifestations
Hypotonia & later spasticity
Lethargy
Ataxia
Deafness + Mutism
Mental retardation
Slow relaxation of deep tendon jerks
 Primary thyroid defect: usually
associated with goiter.
 Secondary to hypothalamic or pituitary
lesions: not associated with goiter.
 2 distinct types of presentation:
 Neurological with MR-deafness & ataxia
 Myxodematous with dwarfism &
dysmorphism
 Early detection by neonatal screening
 High index of suspicion in all infants with
increased risk
 Overt clinical presentation
 Confirm diagnosis by appropriate lab and
radiological tests
 Low (T4, RI uptake & T3 resin uptake)
 High TSH in primary hypothyroidism
 High serum cholesterol & carotene levels
 Anaemia (normo, micro or macrocytic)
 High urinary creatinine/hydroxyproline
ratio
 CXR: cardiomegaly
 ECG: low voltage & bradycardia
Autoimmune Hypothyroidism
Autoimmune hypothyroidism may be associated with a goiter (Hashimoto's,
or goitrous thyroiditis) or, at the later stages of the disease, minimal residual
thyroid tissue (atrophic thyroiditis).
Because the autoimmune process gradually reduces thyroid function, there is a
phase of compensation when normal thyroid hormone levels are maintained by a
rise in TSH. Though some patients may have minor symptoms, this state is
called subclinical hypothyroidism.
Later, unbound T4 levels fall and TSH levels rise further; symptoms become
more readily apparent at this stage (usually TSH >10 mIU/L), which is referred
to as clinical hypothyroidism or overt hypothyroidism.

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Associated conditions
Other Autoimmune disorders:
(MC)
Type 1 diabetes mellitus
Addison's disease
Pernicious anemia
Vitiligo
Alopecia areata
Celiac disease
Dermatitis Herpatiformis
Chronic Active Hepatitis
RA, SLE, Sjogren syndrome
Thyroid associated ophthalmopathy(
in 5% of pt)
Turner syndrome, Down’s syndrome
Type 1 or 2 polyglandular
autoimmune syndrome
Other causes of hypothyroidism
Iatrogenic hypothyroidism is a common cause of hypothyroidism.
In the first 3–4 months after radioiodine treatment, transient hypothyroidism
may occur due to reversible radiation damage. Low-dose thyroxine treatment can
be withdrawn if recovery occurs.
Because TSH levels are suppressed by hyperthyroidism, unbound T4 levels are a
better measure of thyroid function than TSH in the months following radioiodine
treatment.
Mild hypothyroidism after subtotal thyroidectomy may also resolve after several
months, as the gland remnant is stimulated by increased TSH levels.
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 Iodine deficiency is responsible for endemic goiter and cretinism but is an
uncommon cause of adult hypothyroidism unless the iodine intake is very low
or there are complicating factors, such as the consumption of thiocyanates in
cassava or selenium deficiency.
Paradoxically, chronic iodine excess (Rx with amiodarone, lithium) can
also induce goiter and hypothyroidism, individuals with autoimmune thyroiditis
are especially susceptible.
Secondary hypothyroidism is usually diagnosed in the context of other
anterior pituitary hormone deficiencies; isolated TSH deficiency is very rare.
TSH levels may be low, normal, or even slightly increased in secondary
hypothyroidism; the latter is due to secretion of immunoactive but
bioinactive forms of TSH. The diagnosis is confirmed by detecting a low
unbound T4 level.
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 X-ray films can show:
 Delayed bone age or epiphyseal dysgenesis
 Anterior peaking of vertebrae
 Coxavara & coxa plana
 Thyroid radio-isotope scan
 Thyroid ultrasound
 CT or MRI
Myxedema coma
Myxedema coma is defined as severe hypothyroidism leading to decreased
mental status, hypothermia, and other symptoms related to slowing of function in
multiple organs.
It is a medical emergency with a high mortality rate.
There may be a history of treated hypothyroidism with poor compliance, or the
patient may be previously undiagnosed.
Myxedema coma almost always occurs in the elderly and is usually precipitated
by factors that impair respiration, such as drugs (especially sedatives, anesthetics,
antidepressants), pneumonia, congestive heart failure, myocardial infarction,
gastrointestinal bleeding, or cerebrovascular accidents, sepsis.
 L-Thyroxin is the drug of choice. Start with
small dose to avoid cardiac strain.
 Dose is 10 mg/kg/day in infancy. In older
children start with 25 mg/day and increase
by 25 mg every 2 weeks till required dose.
 Monitor clinical progress & hormones level
 Life-long replacement therapy
 5 types of preparations are available:
 L-thyroxin (T4)
 Triiodothyronine (T3)
 Synthetic mixture T4/T3 in 4:1 ratio
 Desiccated thyroid (38mg T4 & 9mg T3/grain)
 Thyroglobulin (36mg T4 & 12mg T3/grain)
1. Peripheral effects:
 BMR
 Deep Tendon Reflex
 Cardiovascular indices (pulse, BP, LV function
tests)
 Serum parameters (high cholesterol, CK, AST,
LDH & carcino-embryonic antigen)
2. Thyroid gland economy:
 Radio iodine uptake
 Perchlorate discharge test (+ve in Pendred
syndrome & autoimmune thyroiditis)
 TSH level
 TRH stimulation tests
 Thyroid scan
3. Tests for thyroid hormone:
 Total & free T4 & T3

 Reverse T3 level

 T3 Resin Uptake
 T3RU x total T4= Thyroid Hormone Binding
Index (formerly Free Thyroxin Index)
 Special Tests:
 Thyroglobulin level
 Thyroid Stimulating Immunoglobulin
 Thyroid antibodies
 Thyroid radio-isotope scan
 Thyroid ultrasound
 CT & MRI
 Thyroid biopsy
Depends on:
Early diagnosis
Proper diabetes education
Strict diabetic control
Careful monitoring
Compliance
 Impaired sensorium, hypoventilation
bradycardia, hypotension & hypothermia
 Precipitated by:
Infections
Trauma (including surgery)
Exposure to cold
Cardio-vascular problems
Drugs
 Is good for linear growth & physical
features even if treatment is delayed, but
for mental and intellectual development
early treatment is crucial.
 Sometimes early treatment may fail to
prevent mental subnormality due to
severe intra-uterine deficiency of thyroid
hormones