THYROID DISORDERS Abdelaziz Elamin. MD, PhD, FRCPCH Professor of Child Health Consultant Pediatric Endocrinologist Sultan Qaboos University, Oman
Dec 22, 2015
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