Download HYPOTHYROIDISM

THYROID DISORDERS
Abdelaziz Elamin. MD, PhD, FRCPCH
Professor of Child Health
Consultant Pediatric Endocrinologist
Sultan Qaboos University, Oman
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:
&
• Grade 1:
• Grade 2:
• Grade 3:
• Grade 4:
Not visible neck extended
Not palpable
Not visible, but palpable
Visible only when neck is
extended & on swallowing,
Visible in all positions
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
75%
Prealbumin TBPA
20%
Albumin TBA
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