This document discusses thyroid disorders, including hypothyroidism. Some key points: - Hypothyroidism affects 1-5 per 1000 live births and is a common cause of preventable mental retardation in children. - It can be congenital or acquired, with causes including iodine deficiency, autoimmune thyroiditis, and medications. - Symptoms include constipation, feeding problems, slow growth, and delayed development. - Diagnosis involves blood tests showing low thyroid hormones and high TSH. Treatment is lifelong thyroid hormone replacement therapy. - Early diagnosis and treatment is important for normal development and intelligence.

1. THYROID DISORDERS
Abdelaziz Elamin. MD, PhD, FRCPCH
Professor of Child Health
Consultant Pediatric Endocrinologist
Sultan Qaboos University, Oman

2. 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

3. ETIOLOGY
• CONGENITAL
Hypoplasia & mal-descent
Familial enzyme defects
Iodine deficiency (endemic cretinism)
Intake of goitrogens during pregnancy
Pituitary defects
Idiopathic

4. ETIOLOGY /2
• ACQUIRED
Iodine deficiency
Auto-immune thyroiditis
Thyroidectomy or RAI therapy
TSH or TRH deficiency
Medications (iodide & Cobalt)
Idiopathic

5. 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

6. 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.

7. 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

8. 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%

9. 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

10. 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

11. 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

12. 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)

13. THYROXINE (T4)
 Total T4 level is decreased in:
Premature infants
Hypopituitarism
Nephrotic syndrome
Liver cirrhosis
PEM
Protein losing entropathy

14. THYROXINE (2)
 Total T4 is decreased when the
following drugs are used:
Steroids
Phenytoin
Salicylates
Sulfonamides
Testosterone
Maternal TBII

15. THYROXINE (3)
 Total T4 is increased with:
Acute thyroiditis
Acute hepatitis
Estrogen therapy
Clofibrate
iodides
Pregnancy
Maternal TSI

16. 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

17. CLINICAL FEATURES
Gestational age > 42 weeks
Birth weight > 4 kg
Open posterior fontanel
Nasal stuffiness & discharge
Macroglossia
Constipation & abdominal distension
Feeding problems & vomiting

18. 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

19. 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

20. CLINICAL FEATURES (5)
• Skeletal abnormalities:
Infantile proportions
Hip & knee flexion
Exaggerated lumbar lordosis
Delayed teeth eruption
Under developed mandible
Delayed closure of anterior fontanel

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

22. 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

23. ASSOCIATIONS
• Autoimmune diseases (Diabetes Mellitus)
• Cardiomyopathy & CHD
• Galactorrhoea
• Muscular dystrophy + pseudohypertrophy
(Kocher-Debre-Semelaigne)

24. GOITROGENS
• DRUGS
Anti-thyroid
Cough medicines
Sulfonamides
Lithium
Phenylbutazone
PAS
Oral hypoglycemic agents

25. GOITROGENS
 FOOD
Soybeans
Millet
Cassava
Cabbage

26. CLINICAL FEATURES (4)
 Neurological manifestations
Hypotonia & later spasticity
Lethargy
Ataxia
Deafness + Mutism
Mental retardation
Slow relaxation of deep tendon jerks

27. 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

28. 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

29. 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

30. 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

31. 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

32. 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)

33. 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)

34. 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

35. 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)

36. THYROID FUNCTION TESTS (4)
 Special Tests:
Thyroglobulin level
Thyroid Stimulating Immunoglobulin
Thyroid antibodies
Thyroid radio-isotope scan
Thyroid ultrasound
CT & MRI
Thyroid biopsy

37. PROGNOSIS
Depends on:
Early diagnosis
Proper diabetes education
Strict diabetic control
Careful monitoring
Compliance

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

39. 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