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: 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 doesnt 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-DebreSemelaigne)

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 g/kg/day in infancy. In older
children start with 25 g/day and increase
by 25 g 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