hypothyroid

THYROID DISORDERS

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

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.
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%
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 Glyco-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

THYROXINE (T4(

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

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
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
OCCASIONAL FEATURES
Overt obesity
Myopathy & rheumatic pains
Speech disorder
Impaired night vision
Sleep apnea (central & obstructive)
Anasarca
Achlorhydria & low intrinsic factor
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


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
Thyroid radio-isotope scan
Thyroid ultrasound
CT or MRI


TREATMENT
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)

THYROID FUNCTION TESTS

Peripheral effects:
BMR
Deep Tendon Reflex
Cardiovascular indices (pulse, BP, LV function tests)
Serum parameters (high cholesterol, CK, AST, LDH & carcino-embryonic antigen)


Thyroid gland economy:
Radio iodine uptake
Perchlorate discharge test (+ve in Pendred syndrome & autoimmune thyroiditis(
TSH level
TRH stimulation tests
Thyroid scan

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


PROGNOSIS
Depends on:
Early diagnosis
Proper diabetes education
Strict diabetic control
Careful monitoring
Compliance
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

MYXOEDMATOUS COMA

Impaired sensorium, hypoventilation bradycardia, hypotension & hypothermia
Precipitated by:
Infections
Trauma (including surgery)
Exposure to cold
Cardio-vascular problems
Drugs