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Cretinism & Hypothyroidism

in ChildrenDr.K.V.Giridhar

Associate Prof. of Pediatrics

GMC. Ananthapuramu, A.P.,India.

• cretinism: ’congenital disease’ due to absence or deficiency of normal thyroid secretion, characterized by physicaldeformity, dwarfism, and mental retardation, and often by goiter.

• Hypothyroidism: ‘acquired disease’ due to primary and other various causes of Thyraoid and hypothalamo, pitutory,thyraoid axis abnormaloties.

Etioliogy of CretinismCONGENITAL

Hypoplasia & mal-descent of thyraoid

Familial enzyme defectsIodine deficiency in pregnacy (endemic cretinism)

Intake of ‘goitrogens’ during pregnancy

Pituitary defectsIdiopathic

Etiology of Hypothyroidism

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

GOITROGENS

• DRUGSAnti-thyroidCough medicinesSulfonamidesLithiumPhenylbutazonePASOral hypoglycemic agents

GOITROGENS

FOODSoybeansMilletsCassavaCabbage

THYROID HORMONESIodine & tyrosine, together

form both, T3 & T4 under TSH stimulation, in thyroid gland.

When released into circulation T4 binds to:Globulin(TBG)-75%Prealbumin(TBPA)-20%Albumin(TBA)- 5%

THYROID HORMONES (c’d)Less than 1% of T4 & T3 is free in

plasma.T4 is deiodinated in the tissues to

either T3 (active)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 for ‘hypothyroidism’.

Thyroid stimulating Hormone (TSH)

Is a Glyco-protein. Secreted by the anterior

pituitary under influence of TRH(TSRH)

It has trophic effect on thyroid gland

It also stimulates, iodine trapping, oxidation, organification, coupling and proteolysis of T4 & T3.

TSH (c’d) T4 & T3 are feed-back regulators

of TSH TSH is stimulated by a-adrenergic

agonists TSH secretion is inhibited by:

DopamineBromocreptineSomatostatinCorticosteroids

Hypothalamo, pituitary, thyraoid Axis

Pituitary gland

Thyroid gland

Hypothalamus

T3

T4

TRH

TSH

THYROID HORMONES (c’d)

Acute & chronic illnessesb-adrenergic receptor blockersStarvation & severe PEMCorticosteroidsPropylthiouracilHigh iodine intake (Wolff-Chaikoff

effect)

Conversion of T4 to T3 is decreased by:

THYROXINE (c’d)

Premature infantsHypo pituitarismNephrotic syndromeLiver cirrhosisPEMProtein losing enteropathy

Total T4 level is decreased in:

THYROXINE (c’d)

SteroidsPhenytoinSalicylatesSulfonamidesTestosteroneMaternal TBIgs.

Drugs, which decrease Total T4:

THYROXINE (c’d)

Acute thyroiditisAcute hepatitisEstrogen therapyClofibrateiodidesPregnancyMaternal TSH

Total T4 is increased with:

FUNCTIONS OF THYROXINE Thyroid hormones are essential for:

Linear growth & pubertal development

Normal brain development & function

Energy productionCalcium mobilization from boneIncreasing sensitivity of b-adrenergic receptors to catecholeamines

CLINICAL FEATURES

Birth weight > 4 kgOpen posterior fontanelNasal stuffiness & dischargeMacroglossiaConstipation & abdominal

distensionFeeding problems & vomiting

CLINICAL FEATURES (c’d)Non pitting edema of limbs Coarse featuresUmbilical herniaHoarseness of voiceAnemiaDecreased physical activityProlonged (>3 weeks)

neonatal jaundice

CLINICAL FEATURES (c’d)

Dry, pale & mottled skinLow hair line & dry, scanty

hairHypothermia & peripheral

cyanosisHypercarotenemiaGrowth failureRetarded bone ageStumpy fingers & broad hands

CLINICAL FEATURES (c’d)Skeletal abnormalities:

Infantile proportionsHip & knee flexionExaggerated lumbar lordosis

Delayed 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 (c’d)Decreased bone turnoverDecreased VIII, IX & platelets

adhesionDecreased GFR &

hyponatremiaHypertensionIncreased levels of CK,LDH &

AST Abnormal EEG & high CSF

proteinPsychiatric manifestations

CLINICAL FEATURES (c’d)

Neurological manifestationsHypotonia & later spasticityLethargyAtaxiaDeafness + MutismMental retardationSlow relaxation of deep tendon jerks

ASSOCIATIONS

Autoimmune diseases Diabetes MellitusCardiomyopathy & CHDGalactorrhoeaMuscular dystrophy + pseudo hypertrophy (Kocher-Debre-Semelaigne Syndrome)

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 TESTS

Low (T4& T3)High TSHHigh 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 dysgenesis

Anterior beaking of vertebraeCoxavara & coxa plana

Thyroid radio-isotope scan Thyroid ultrasound CT or MRI

THYROID FUNCTION TESTS(c’d)

Specific Tests:Thyroglobulin levelThyroid Stimulating

ImmunoglobulinThyroid antibodiesThyroid radio-isotope scanThyroid ultrasoundCT & MRIThyroid biopsy

TREATMENT L-Thyroxin is the drug of

choice. Start with small dose.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(c’d) 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)

PROGNOSIS

Depends on:Early diagnosis

Proper counselling

Strict diet control

Careful monitoring

Compliance

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 also fail, to prevent mental sub normality due to severe intra-uterine deficiency of thyroid hormones

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