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

HYPOTHYROIDISM-EPIDEMIOLOGYNeonatal screening reveals incidence that varies between 1-5/1000 live birthsThe most common cause of preventable mental retardation in childrenBoth acquired & congenital forms are linked to iodine deficiencyDiagnosis is easy & early treatment is beneficial

ETIOLOGYCONGENITALHypoplasia & mal-descentFamilial enzyme defectsIodine deficiency (endemic cretinism)Intake of goitrogens during pregnancyPituitary defectsIdiopathic

ETIOLOGY /2ACQUIREDIodine deficiencyAuto-immune thyroiditisThyroidectomy or RAI therapyTSH or TRH deficiencyMedications (iodide & Cobalt)Idiopathic

KILPATRIK GRADING OF GOITREGrade 0:Not visible neck extended &Not palpableGrade 1:Not visible, but palpableGrade 2:Visible only when neck is extended & on swallowing,Grade 3:Visible in all positionsGrade 4:Large goiter

THYROID GLANDDerived from pharyngeal endoderm at 4/40Migrate 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 HORMONESIodine & 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:GlobulinTBG 75%PrealbuminTBPA 20%AlbuminTBA 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 & feetCoarse featuresUmbilical herniaHoarseness of voiceAnemiaDecreased physical activityProlonged (>2/52) neonatal jaundice

CLINICAL FEATURES (3)Dry, pale & mottled skinLow hair line & dry, scanty hairHypothermia & peripheral cyanosisHypercarotenemiaGrowth failureRetarded bone ageStumpy fingers & broad hands

CLINICAL FEATURES (5)Skeletal abnormalities:Infantile proportionsHip & knee flexionExaggerated lumbar lordosisDelayed teeth eruptionUnder developed mandibleDelayed closure of anterior fontanel

OCCASIONAL FEATURESOvert obesityMyopathy & rheumatic painsSpeech disorderImpaired night visionSleep apnea (central & obstructive)AnasarcaAchlorhydria & low intrinsic factor

OCCASIONAL FEATURES (2)Decreased bone turnoverDecreased VIII, IX & platelets adhesionDecreased GFR & hyponatremiaHypertensionIncreased levels of CK, LDH & AST Abnormal EEG & high CSF proteinPsychiatric manifestations

ASSOCIATIONSAutoimmune diseases (Diabetes Mellitus)Cardiomyopathy & CHDGalactorrhoeaMuscular dystrophy + pseudohypertrophy (Kocher-Debre-Semelaigne)

GOITROGENSDRUGSAnti-thyroidCough medicinesSulfonamidesLithiumPhenylbutazonePASOral hypoglycemic agents

GOITROGENS FOODSoybeansMilletCassavaCabbage

CLINICAL FEATURES (4) Neurological manifestationsHypotonia & later spasticityLethargyAtaxiaDeafness + MutismMental retardationSlow relaxation of deep tendon jerks

CONGENITAL HYPOTHYRODISMPrimary 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

DIAGNOSISEarly detection by neonatal screeningHigh index of suspicion in all infants with increased riskOvert clinical presentationConfirm diagnosis by appropriate lab and radiological tests

LABROTARY FINDINGSLow (T4, RI uptake & T3 resin uptake)High TSH in primary hypothyroidismHigh serum cholesterol & carotene levelsAnaemia (normo, micro or macrocytic)High urinary creatinine/hydroxyproline ratioCXR: cardiomegalyECG: 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 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

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 TESTS1. Peripheral effects:BMRDeep Tendon ReflexCardiovascular 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 levelTRH stimulation testsThyroid scan

THYROID FUNCTION TESTS (3)3. Tests for thyroid hormone:Total & free T4 & T3Reverse T3 levelT3 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

PROGNOSISDepends on:Early diagnosisProper diabetes educationStrict diabetic controlCareful monitoringCompliance

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