THYROID DISORDERSAbdelaziz Elamin. MD, PhD, FRCPCHProfessor of Child HealthConsultant Pediatric EndocrinologistSultan 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

•CONGENITALHypoplasia & mal-descentFamilial enzyme defectsIodine deficiency (endemic cretinism)Intake of goitrogens during

pregnancyPituitary defectsIdiopathic

ETIOLOGY /2

•ACQUIREDIodine deficiencyAuto-immune thyroiditisThyroidectomy or RAI therapyTSH or TRH deficiencyMedications (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 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:

DopamineBromocreptineSomatostatinCorticosteroids

THYROID HORMONES (3)

Conversion of T4 to T3 is decreased by:Acute & chronic illnessesb-adrenergic receptor blockersStarvation & severe PEMCorticosteroidsPropylthiouracilHigh iodine intake (Wolff-Chaikoff effect)

THYROXINE (T4)

Total T4 level is decreased in:Premature infantsHypopituitarismNephrotic syndromeLiver cirrhosisPEMProtein losing entropathy

THYROXINE (2) Total T4 is decreased when the

following drugs are used:SteroidsPhenytoinSalicylatesSulfonamidesTestosteroneMaternal TBII

THYROXINE (3) Total T4 is increased with:

Acute thyroiditisAcute hepatitisEstrogen therapyClofibrateiodidesPregnancyMaternal TSI

FUNCTIONS OF THYROXINE

Thyroid hormones are essential for:Linear growth & pubertal developmentNormal brain development & functionEnergy productionCalcium mobilization from boneIncreasing sensitivity of b-adrenergic

receptors to catecholeamines

CLINICAL FEATURESGestational age > 42 weeksBirth weight > 4 kgOpen posterior fontanelNasal stuffiness & dischargeMacroglossiaConstipation & abdominal

distensionFeeding 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 proportionsHip & knee flexionExaggerated lumbar lordosisDelayed teeth eruptionUnder developed mandibleDelayed 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-thyroidCough medicinesSulfonamidesLithiumPhenylbutazonePASOral hypoglycemic agents

GOITROGENS

FOODSoybeansMilletCassavaCabbage

CLINICAL FEATURES (4)

Neurological manifestationsHypotonia & later spasticityLethargyAtaxiaDeafness + MutismMental retardationSlow 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 & ataxiaMyxodematous 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

dysgenesisAnterior peaking of vertebraeCoxavara & 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 ratioDesiccated 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 levelThyroid Stimulating ImmunoglobulinThyroid antibodiesThyroid radio-isotope scanThyroid ultrasoundCT & MRIThyroid 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:InfectionsTrauma (including surgery)Exposure to coldCardio-vascular problemsDrugs

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