CONGENITAL HYPOTHYROIDISM IS MOST COMMON PREVENTABLE CAUSE OF MENTAL RETARDATION THING TO KNOW ABOUT CH

1. CONGENITAL HYPOTHYROIDISM
DR MAHTAB
FELLOW, FORTIS LAFEMME

2. INTRODUCTION
 CONGENITAL HYPOTHYROIDISM IS COMMONEST CAUSE OF PREVENTABLE MENTAL
RETARDATION
 INCIDENCE
WORLD WIDE 1:3000-4000 LIVE BIRTH
INDIA 1:1200-3400 LIVE BIRTH
EARLY DETECTION AND TREATMENT OF CH THROUGH NEONATAL SCREENING PREVENT
NEURO DEVELOPMENTAL DISABILITY AND OPTIMIZE DEVELOPMENTAL OUTCOME
 NBS FOR CH SHOULD BE DONE FOR EVERY NEW BORN IN INDIA
JCEM ( EUROPEAN SOCIETY FOR PEDIATRIC ENDOCRINOLOGY)

3. INDICATION FOR SCREENING
IN ABSENCE OF FACILITY OF UNIVERSAL SCREENING
 1. FAMILY HISTORY OF CH
 2. H/O THYROID DISEASE OR ANTI THYROID MEDICINE INTAKE IN MOTHER
 3. PRESENCE OF OTHER CONDITION LIKE
DOWN SYNDROME,TRISOMY 18,NTD,CHD,METABOLIC DISORDER,FAMILIAL
AUTOIMMUNE DISORDER,AND PIERRE- ROBIN SYNDROME
ANY INFANT WITH SIGN AND SYMPTOM OF HYPOTHYROIDISM

4. CLINICAL FEATURE
 POST MATURITY,MACROSOMIA, OR WIDE OPEN POSTERIOR
FONTANEL
PROLONG JAUNDICE,CONSTIPATION,POOR
FEEDING,HYPOTONIA,HOARSE CRY,
UMBILICAL HERNIA,MACROGLOSSIA,OR DRY EDEMATOUS SKIN,

5. CLINICAL
FEATURE

8. ETIOLOGY
ETIOLOGY CAN BE PERMANENT OR TRANSIENT
1. PERMANENT HYPOTHYROIDISM:
THYROID DYSGENESIS( APLASIA,HYPOPLASIA,ECTOPIA)
THYROID HORMONE BIOSYNTHETIC DEFECT
HYPOTHALAMIC PITUITARY HYPOTHYROIDISM
2. TRANSIENT HYPOTHYROIDISM
ENDEMIC IODINE DEFICIENCY
TSH BINDING INHIBITORY IMMUNOGLOBIN
EXPOSURE TO GOITROGEN (IODINES,ANTI THYROID DRUG )
MATERNAL ANTI THYROID MEDICATION
DUOX2 MUTATION ISOLATED HYPERTHYROTROPINEMIA (NORMAL T4 AND HIGH TSH )
OTHERS; MATERNAL HYPERTHYROIDISM,TRANSIENT HYPOTHYROXINEMIA OF NEW BORN,DRUGS:
DOPAMINE,STEROID, SICK EUTHYROID SYNDROME

9. WHEN TO SCREEN
 NORMAL HOSPITAL DELIVERY AT TERM: FILTER PAPER COLLECTION
IDEALLY AT 2-4 DAY OF AGE OR AT TIME OF DISCHARGE
 NICU/PRETERM HOME BIRTH: WITHIN 7 DAYS OF BIRTH
 MATERNAL HISTORY OF THYROID MEDICATION/FAMILY H/O CH:
CORD BLOOD FOR SCREENING

10. CORD BLOOD Vs POST NATAL SAMPLE
 TSH SURGE START 30 MIN AFTER BIRTH ,MOST MARKED FOR NEXT 24 HOUR,MAY PERSIST
FOR 48-72 HR
 SO FALSE POSITIVE INCREASE
 SO EITHER CORD SAMPLE OR POST NATAL > 72 HR
 LBW,VLBW,SICK NEONATES,MULTIPLE BIRTHS PARTICULAR SAME SEX INCREASED RISK OF
INAPPROPRIATE TSH ( BOTH FALSE POSITIVE & FALSE NEGATIVE) SO TEST AT 48-72 HR POST
NATAL AGE,NOT EARLIER
 ONLY IN INSTANCES OF ACUTE HEMOLYSIS ,WHEN TRASFUSION WARRANTED SCREEN
BEFORE 24-48 HR
 SICK INFANT IN NICU ATLEAST BY 7 DAYS

11.  CORD SAMPLE
ADVANTAGES : PAINLESS, LARGE QUANTITY AVALIEBLE,NOT EFFECTED BY NEONATAL SURGE
DISADVANTAGES : METABOLIC DISORDER DEPEND UPON FEEDING CAN NOT BE TESTED,24 HR
TRAINED PERSON REQUIRED, AFFECTED BY PERINATAL FACTOR EG BIRTH ASPHYXIA
POST NATAL SAMPLE:
ADVANTAGES: OTHER DISORDER CAN BE TESTED LIKE CAH ,THOSE DEPENDENT ON FEEDING (
GALACTOSEMIA,PKU),TRAINING OR LOGISTIC NEEDED FOR MORNING SHIFT, CAN BE DONE FOR
BABIES DELIVERED AT HOME
DISADVANTAGES; PAIN TO BABY,FALSE POSITIVE IN CASE OF EARLY DISCHARGE
EITHER SERUM OR FILTER PAPER THYROID HORMONE ASSAY SHOULD BE USED FOR SCREEN FOR
CH,THE CHOICE OF METHOD DEPEND UPON LOCAL FACILITIES

12. APPROACHES TO SCREEN CH
 THREE APPROACHES
1. PRIMARY TSH ,BACK UP T4 : FIRST TSH IS MEASURED T4 IS MEASURED WHEN TSH > 20mU/L
MOST WIDELY USED, MOST SENSATIVE AND COST EFFECTIVE
BUT LIKELY TO MISS CENTRAL HYPOTHYROIDISM, THYROID BINDING GLOBULIN (TBG)
DEFICIENCY,HYPOTHYROXINEMIA WITH DELAYED TSH ELEVATION
2. PRIMARY T4 ,BACK UP TSH: FIRST T4 IF LOW THAN TSH
BUT LIKELY TO MISS MILDER AND SUB CLINICAL CASES OF CH IN WHICH T4 INITIALLY NORMAL WITH
TSH ELEVATION
3. CO COMITENT T4 & TSH: IDEAL BUT HIGHER COST
FIRST ONE IS WIDELY USED INFACT ISPAE RECOMMEND THIS

13. CONDUCT OF TSH BASED SCREENING
 MEASUREMENT OF DBS AND SERUM UNIT IS SAME
 SERUM UNIT DERIVED BY MULTIPLYING THE WHOLE BLOOD UNIT BY 2.2
 FOR UNIFORM USE RECOMMMEND SERUM UNIT FOR ALL
ISPAE 2018

14.  REFERENCE RANGE OF SERUM FREET4 AND TSH
PEDIATRIC ENDOCRINOLOGY 2ND EDITIONPHILIDELPHIA 2002
AGE IN WEEKS FREE T4(ng/dL ) TSH (mu/L)
25-27 0.6-2.2 0.2-30.3
28-30 0.6-3.4 0.2-20.6
31-33 1.0-3.8 0.7-20.9
34-36 1.2-4.4 1.2-21.6

15. REFERENCE RANGE FOR T4 AND TSH IN TERM INFANT
AGE T4(microgram/dL)
MEAN(RANGE)
F t4 (pg/ml )
MEAN(SD)/RANGE
TSH (Mu/l)
MEAN(SD)/MEADIAN(
ANGE)
CORD BLOOD 10.8 (6.6-15) 13.8 10.0
1-3 DAYS 16.5(11-21.5) 1.4(0.04) 5.6(1-10)
4-7 DAY 11.3(0.3) 22.3(3.9) 6.0(0.6)
1-2 WEEKS 12.7(8.2-17.2) 1.3(0.03) 2.3(0.5-6.5)
2-4 WEEKS 10.1(0.6) 0.9-2.2 3.9(0.4)
4 WEEKS -12 MONTH 11.1(5.9-13) 15.5(14.0-17.2) 2.8(1.9-4.4)

18. TSH CUT OFF FOR SCREENING TEST
 TSH > 20mIU/L RECALL FOR CORD BLOOD AND POST NATAL SCREEN SAMPLE AFTER
48 HOUR OF AGE
 TSH >40 m IU/L IS RECOMMEND FOR DEFINING SCREEN POSITIVE CASES FOR
IMMEDIATE RECALL(AFTER 72 HR) FOR VENOUS CONFIRMATORY TEST
WHERE MILDLY ELEVATED FROM 20-40 m IU/L SHOULD HAVE SECOND
TSH SCREEN AT 7-10 DAY OF AGE
AGE RELATED TSH CUT-OFF > 34m IU/L IS SUGGESTED FOR SCREEN SAMPLE TAKEN
BETWEEN 24-48 HOUR OF AGE
ISPAE 2018

19.  IN BIRMINGHAM CHILDREN HOSPITAL
CH SCREENING INCLUDED IN ROUTINE NEONATAL BLOOD SPOT SCREENING
AT DAY 5-8 DAYS
IN PRETERM < 31+6 REPEAT AT 28TH DAY OR AT DISCHARGE
TSH<10 m U/L NEGATIVE
10-20 BORDERLINE
> 20 POSITIVE
REPEAT TSH RESULT IS
< 10 CH NOT SUSPECTED
> 10 CH SUSPECTED

20. WHEN WE ASK FOR FREE T4 LEVEL
 FREE T4 IS DEFINITELY ESTIMATED
1. PRE MATURE AND SICK NEW BORN: BCZ ABNORMAL PROTEIN BINDING OR
LOW LEVEL TBG DUE IMMURITY OF LIVER
2. LOW T4 & NORMAL TSH: IF FREE T4 IS NORMAL SO IT MAY A CASE OF
PARTIAL OR COMPLETE TBG DEFICIENCY
TBG LEVEL SHOULD BE EVALUATED TO CONFIRM THIS
IF FREE T4 LEVEL IS LOW ALONG WITH LOW T4 WITH NORMAL TSH THAN
CENTRAL HYPOTHYROIDISM SHOULD SUSPECTED
3. MONITOR OF ADEQUECY OF TREATMENT

21. SPECIAL SITUATION
 ALL NEW BORN ,PRETERM AND LBW/VLBW SHOULD UNDERGO ROUTINE
SCREENING FOR CH ONLY AT 48-72 HR POST NATAL AGE
 IN ACUTE HEMORRHAGE OR HEMOLYSIS WHEN TRANSFUSION
WARRANTED SCREEN BEFORE 24-48 HR
 SICK INFANT IN NICU SCREEN SHOULD BE PERFORM BY 7 DAY
 SECOND SCREENING TEST AT 2-4 WK OF AGE FOR HIGH RISK BABIES
 TSH CUT OFF REMAIN SAME AS FOR TERM BABIES

23. DECISION MAKING FOR BORDERLINE
TFT
 ELEVATED TSH AND NORMAL FT4 LEVEL,BABY RETESTED AFTER 2 WEEK
 AFTER 3 WEEK IF TSH REMAIN PERSISTENTLY >10m IU/L EVEN NORMAL
T4/FT4 , LEVOTHYROXINE STARTED
 REFERRAL PEDIATRIC ENDOCRINOLOGIST IS SUGGESTED FOR ALL BABY
OF CH INCLUDING BORDERLINE RESULT

24. EVALUATION
 MATERNAL:
POSSIBLE MATERNAL THYROID DISEASE/MEDICATION
DETAIL OF MATERNAL DIET DURING PREGNANCY
FAMILY HISTORY OF THYROID DIEASES OR DEAFNESS
INFANT:
CLINICAL FEATURE S/O CH
EXAMINE BABY FOR GOITRE
GROWTH PARAMETER
A/W OTHER CONGENITAL ABNORMALITIES EG CHD 10% Vs 3% ESPECIALLY
PS,ASD,VSD

25. INVESTIGATION
 TSH AND FREET4
 TSB IF BABY HAVING SIGNIFICANT JAUNDICE
 THYROID SCAN (IOC)
 X RAY OF THE KNEE: ABSENCE OF EPIPHYSIS MAY REFLECT THE DEGREE OF
INTRAUTERINE HYPOTHYROIDISM
 MATERNAL AND INFANT ANTITHYROID ANTIBODIES IF H/O MATERNAL AUTO
IMMUNE THYROID DISEASE
TSH RECEPTOR MEASUREMENT IS PREFERABLE
IF ABSENT THAN ANTI THYROGLOBIN AND ANTI THYROID PEROXIDASE A/B
…SHOW MATERNAL TRANSMISSON
 HEARING ASSESSMENT : IN SUSPECTED DYSHORMOGENESIS
APEG/EUROPEAN SOCIETY OF PEDIATRIC ENDOCRINOLOGY

26.  THYROID SCAN
 INVESTIGATION OF CHOICE
 STRONGLY ADVISED GIVE CLEAR CUT DIAGNOSIS
 PERFORM BY TECHNETIUM -99m
 SCAN CAN BE PERFORM AFTER WITHIN A FEW DAYS OF STARTING THERAPY( UP TO 5 DAYS)
 ABSENT ISOTOPE UPTAKE MEANS AGENESIS OF THYROID GLAND MAY CAUSED BY MATERNAL BLOCKI
ANTIBODIES
 UPTAKE REDUCED OR ABNORMAL POSITION : HYPOPLASTIC OR ECTOPIC GLAND
 INCREASED UPTAKE AT NORMAL POSITION INDICATES DEFECT OF THYROXINE BIO
SYNTHESIS,DYSHORMOGENESIS OR EXCESSIVE EXPOSURE TO IODINE

27. BIOCHEMICAL CRITERIA TO INITIATE
THERAPY
 IF CAPILLARY TSH CONCENTRATION >40m U/L VENOUS SAMPLE SENT TFT TREATMENT START
 < 40 m U/L CLINICIAN WAIT OF VENOUS TFT
DECISION ON BASIS OF VENOUS TFTS
IF VENOUS FREE T4 CONC BELOW NORMAL RANGE TREATMENT START IMMEDIATELY
IF TSH >20m U/L ,FT4 NORMAL TREATMENT STARTED
TSH 6-20m U/L WELL BABY WITH NORMAL T4 DO DIAGNOSTIC IMAGING FOR DEFINITE DIAGNOSIS,
DISCUSS WITH FAMILY IMMEDIATE TREATMENT OR RETESTING AFTER 2 WEEK
JCEM (EUROPEAN SOCIETY OF PEDIATRIC ENDOCRINOLOGY)

28. TREATMENT
 STARTED AS SOON AS POSSIBLE AS CH IS CONFIRMED BY TFT
 THYROXINE @10 MICROGRAM/KG/DAY
 TAB IS CRUSHED AND MIX WITH LITTLE MILK OR WATER
 DOSAGE IS ADJUSTED ACCORDING TO TFT AIMING KEEP FREE T4 AT UPPER END
OF NORMAL RANGE AND TSH SUPPRESS INTO NORMAL RANGE
APEG (AUSTRALIAN PEDIATRIC ENDOCRINE GROUP)

29. TREATMENT CONTINUE
 INITIAL L -T4 DOSE OF 10-15 MICROGRAM/KG/DAY
 SEVERE DISEASE HIGHEST DOSE
 ORALLY IF IV 80% OF ORAL DOSE THAN ADJUSTMENT A/P TFT
JCEM ( EUROPEAN SOCIETY FOR PEDIATRIC ENDOCRINOLOGY)

30. COMMON DOSAGE
0-6 MONTH 25-50 MICROGRAM/DAY 8-15MICGRAM/KG/DAY
6-12 50-75 7-10
1-5 YR 50-100 5-7
5-10 YR 100-150 3-5
> 10-12 YR 100-200 2-4

31. FOLLOW UP
 AT 2 WEEKS,SIX WEEKS,3MONTH, AND THAN 2-3 MONTHLY DURING THE FIRST YEAR.
THEREAFTER AT THREE MONTHLY INTERVAL UNTIL 2-3 YEARS THAN 4 MONTHLY
TFT REPEAT VISIT AND DOSE ADJUSTED
TFT SHOULD BE DETERMINED ATLEAST 4 HOUR AFTER LAST L-T4 DOSE
MOST FREQUENT EVALUATION SHOULD BE CARRIED OUT IF COMPLIANCE QUESTIONED OR ABNORMAL
VALUEOBTAINED
ADDITIONAL EVALUATION AFTER 4-6 WEEKS AFTER ANY CHANGE IN L-T4 DOSE
GROWTH AND DEVELOPMENT MUST BE CLOSELY MONITORED
 APEG/
JCEM ( EUROPEAN SOCIETY FOR PEDIATRIC ENDOCRINOLOGY)

32.  HEARING ASSESSMENT:
 ALL BABY WITH SUSPECTED DYSHORMONOGENESIS (F/O PENDARD SYNDROME AND
THYROID SCAN FINDING AS ABOVE
 BERA OR OAE @ 4-8 WEEKS. THEREAFTER TESTING SHOULD BE REPEATED 3 MONTHLY
ATLEAST FOR 1ST YEAR BABY WITH DYSHORMOGENESIS
 DEVELOPMENTAL ASSESSMENT ( AT 18-24 MONTHS AND PRE SCHOOL SUGGESTED USEFUL
TIME
 SUSPECTED TRANSIENT CH SHOULD BE TRIED OFF THERAPY @3 YEAR,OR ALLOW TO GROW
OUT OF THEIR DOSES
APEG

33. OVER TREATMENT OF THYROID
 MAY CAUSE CRANIOSYNTOSIS,ACCELERATED GROWTH AND MATURATION,DISTURB SLEEP
PATTERN,ALTERED TEMPO OF BRAIN MATURATION,MORE BEHAVIOUR PROBLEMS ( SOCIAL
WITHDRAWAL,HYPERACTIVITY,CONDUCT PROBLEM AND ANXIETY
IN CHILDREN INITRIAL DOSE IS > 10 MICROGRAM/KG/DAY
SEEM 8-12 MICROGRAM/KG/DAY IS PRUDENT
IN SEVERE CH MAY 15 MICROGRAM/KG/DAY WITH CAREFUL MONITORING
 12. Rovet J, Ehrlich R, Sorbara D. Intellectual outcome in children with fetal hypothyroidism. J
Pediatr 1987; 110: 700 - 4.

34. COUNSELLING
 REASSURED ABOUT FAVOURABLE PROGNOSIS: NORMAL ,HEALTHY ADULT WITH
NORMAL INTELLIGENCE
 THYROIS DYSGENESIS: VERY UNLIKELY TO RECURR IN SUBSEQUENT CHILD
 DYSHORMONOGENESIS LIKELY TO BE AR INHERITENCE WITH A RISK OF 1:4 RISK
OF RECURRENCE
APEG

35. ANTE NATAL DIAGNOSIS,SCREENING,POTENTIAL
TREATMENT
 WHEN GOITRE IS FORTUITOUSLY DISCOVERED DURING FETAL ULTRASOUND,WITH F/O
DYSHORMOGENESIS
 CORDOCENTESIS DONE TO ASSESS FETAL TFT
 A LARGE GOITRE IN FETUS WITH PROGRESSIVE POLY HYDRAMNIOS AND RISK OF
PREMATURE LABOUR AND /OR CONCERN ABOUT TRACHEAL OBSTRUCTION
 INTRA AMNIOTIC L-T4 INJECTION SHOULD BE FOLLOWED IN MULTIDISPLINARY
SPECIALIST TEAM