Transcript HYPOTHYROIDISM

Dr.mirzarahimi
HYPOTHYROIDISM-EPIDEMIOLOGY
 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
ETIOLOGY
CONGENITAL
Hypoplasia & mal-descent
Familial enzyme defects
Iodine deficiency (endemic cretinism)
Intake of goitrogens during pregnancy
Pituitary defects
Idiopathic
ETIOLOGY /2
ACQUIRED
Iodine deficiency
Auto-immune thyroiditis
Thyroidectomy or RAI therapy
TSH or TRH deficiency
Medications (iodide & Cobalt)
Idiopathic
KILPATRIK GRADING OF GOITRE
 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
THYROID GLAND
 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.
OVERVIEW (2)
 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
THYROID HORMONES
 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
Prealbumin
TBPA
Albumin TBA
75%
20%
5%
THYROID HORMONES (2)
 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
TSH
 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
TSH (2)
 T4 & T3 are feed-back regulators of TSH
 TSH is stimulated by a-adrenergic agonists
 TSH secretion is inhibited by:
Dopamine
Bromocreptine
Somatostatin
Corticosteroids
THYROID HORMONES (3)
 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)
THYROXINE (T4)

Total T4 level is decreased in:
Premature infants
Hypopituitarism
Nephrotic syndrome
Liver cirrhosis
PEM
Protein losing entropathy
THYROXINE (2)
 Total
T4 is decreased when the
following drugs are used:
Steroids
Phenytoin
Salicylates
Sulfonamides
Testosterone
Maternal TBII
THYROXINE (3)
 Total T4 is increased with:
 Acute thyroiditis
 Acute hepatitis
 Estrogen therapy
 Clofibrate
 iodides
 Pregnancy
 Maternal TSI
FUNCTIONS OF THYROXINE
 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
CLINICAL FEATURES
 Gestational age > 42 weeks
 Birth weight > 4 kg
 Open posterior fontanel
 Nasal stuffiness & discharge
 Macroglossia
 Constipation & abdominal distension
 Feeding problems & vomiting
CLINICAL FEATURES (2)
 Non pitting edema of lower limbs & feet
 Coarse features
 Umbilical hernia
 Hoarseness of voice
 Anemia
 Decreased physical activity
 Prolonged (>2/52) neonatal jaundice
CLINICAL FEATURES (3)
 Dry, pale & mottled skin
 Low hair line & dry, scanty hair
 Hypothermia & peripheral cyanosis
 Hypercarotenemia
 Growth failure
 Retarded bone age
 Stumpy fingers & broad hands
CLINICAL FEATURES (5)
 Skeletal abnormalities:
Infantile proportions
Hip & knee flexion
Exaggerated lumbar lordosis
Delayed teeth eruption
Under developed mandible
Delayed closure of anterior fontanel
OCCASIONAL FEATURES
 Overt obesity
 Myopathy & rheumatic pains
 Speech disorder
 Impaired night vision
 Sleep apnea (central & obstructive)
 Anasarca
 Achlorhydria & low intrinsic factor
OCCASIONAL FEATURES (2)
 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
ASSOCIATIONS
 Autoimmune diseases (Diabetes Mellitus)
 Cardiomyopathy & CHD
 Galactorrhoea
 Muscular dystrophy + pseudohypertrophy (Kocher-
Debre-Semelaigne)
GOITROGENS
 DRUGS
Anti-thyroid
Cough medicines
Sulfonamides
Lithium
Phenylbutazone
PAS
Oral hypoglycemic agents
GOITROGENS
 FOOD
Soybeans
Millet
Cassava
Cabbage
CLINICAL FEATURES (4)
 Neurological manifestations
Hypotonia & later spasticity
Lethargy
Ataxia
Deafness + Mutism
Mental retardation
Slow relaxation of deep tendon jerks
CONGENITAL HYPOTHYRODISM
 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
DIAGNOSIS
 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
LABROTARY FINDINGS
 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
IMAGING TESTS
 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
TREATMENT (2)
 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
TREATMENT
 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)
THYROID FUNCTION TESTS
1. Peripheral effects:
 BMR
 Deep Tendon Reflex
 Cardiovascular indices (pulse, BP, LV function tests)
 Serum parameters (high cholesterol, CK, AST, LDH &
carcino-embryonic antigen)
THYROID FUNCTION TESTS (2)
2. Thyroid gland economy:
 Radio iodine uptake
 Perchlorate discharge test (+ve in Pendred syndrome
& autoimmune thyroiditis)
 TSH level
 TRH stimulation tests
 Thyroid scan
THYROID FUNCTION TESTS (3)
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)
THYROID FUNCTION TESTS (4)
 Special Tests:
 Thyroglobulin level
 Thyroid Stimulating Immunoglobulin
 Thyroid antibodies
 Thyroid radio-isotope scan
 Thyroid ultrasound
 CT & MRI
 Thyroid biopsy
PROGNOSIS
Depends on:
Early diagnosis
Proper diabetes education
Strict diabetic control
Careful monitoring
Compliance
MYXOEDMATOUS COMA
 Impaired sensorium, hypoventilation bradycardia,
hypotension & hypothermia
 Precipitated by:
Infections
Trauma
(including surgery)
Exposure to cold
Cardio-vascular problems
Drugs
PROGNOSIS
 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