NEONATE BORN TO MOTHER NEONATE BORN TO MOTHER WITH GRAVE’S DISEASEWITH GRAVE’S DISEASE

Baby boy born at 24 weeks gestation, Baby boy born at 24 weeks gestation, weight 559Gweight 559G

Mother 25year,G6 P4 Ab1 LC4.Mother 25year,G6 P4 Ab1 LC4.

Known case of Grave’s disease, with Known case of Grave’s disease, with uncontrolled thyrotoxicosis since 1999…non uncontrolled thyrotoxicosis since 1999…non compliant on treatment (PTU/Inderal). No compliant on treatment (PTU/Inderal). No PNC.PNC.

With pre-eclampsia, abruption- severe With pre-eclampsia, abruption- severe decelerations-Emergency C-sectiondecelerations-Emergency C-section..

NICU COURSENICU COURSE Maternal TSI on Sept 2003: 212% Maternal TSI on Sept 2003: 212% (Normal 0 - 129%)(Normal 0 - 129%)• Resuscitated at birth Apgars 3,6 & 8.Ventilated Resuscitated at birth Apgars 3,6 & 8.Ventilated

….given curosurf and transferred to ICN on ….given curosurf and transferred to ICN on portable ventilatorportable ventilator

• On exam, baby 24 weeks gestation AGAOn exam, baby 24 weeks gestation AGA

Systemic exam WNL. No evidence of Systemic exam WNL. No evidence of goiter/exophthalmos. Initially had heart rates in goiter/exophthalmos. Initially had heart rates in 160-170 but later normalized160-170 but later normalized..

MANAGEMENT IN NICUMANAGEMENT IN NICU

Hypoperfusion/hypotension/metabolic Hypoperfusion/hypotension/metabolic acidosis needing NS bolus x 2 and acidosis needing NS bolus x 2 and inotrope support.inotrope support.

D2-3 echo showed PDA…treated with D2-3 echo showed PDA…treated with IndomethacinIndomethacin

Head sono…no IVH. Drug screen normalHead sono…no IVH. Drug screen normal

THYROID CHEMISTRIESTHYROID CHEMISTRIES

Infant valuesInfant values Day -1Day -1 Day -7Day -7

T4,freeT4,free

(0.6-1.70)(0.6-1.70)

1.261.26 0.450.45

TSHTSH

(0.4-5)(0.4-5)

0.070.07 0.010.01

T3,totalT3,total

(70-204)(70-204)

124124 9797

PRESENT CONDITIONPRESENT CONDITION

Presently baby on IMV, being treated for Presently baby on IMV, being treated for evolving lung disease…diuretics and steroid evolving lung disease…diuretics and steroid nebulizationnebulization

On TPN and NG feeds.On TPN and NG feeds.

OBSTETRIC HISTORYOBSTETRIC HISTORY

7/96 40wks 9lbs NSVD Dallas7/96 40wks 9lbs NSVD Dallas 9/97 40wks 7lbs NSVD Mexico9/97 40wks 7lbs NSVD Mexico 11/01 31wks 2lbs NSVD Thomason11/01 31wks 2lbs NSVD Thomason 9/03 36wks 3lbs NSVD Thomason9/03 36wks 3lbs NSVD Thomason 12/00 15wks miscarriage12/00 15wks miscarriage 7/04 24wks 1.2lbs CS Thomason7/04 24wks 1.2lbs CS Thomason

BABY WITH NEONATALBABY WITH NEONATALTHYROTOXICOSISTHYROTOXICOSIS

Baby No.3 was born at Thomason in 2001Baby No.3 was born at Thomason in 2001 Preterm 31 wks SGA , BW:1130 GPreterm 31 wks SGA , BW:1130 G No prenatal-care. Presented 1 hour prior to No prenatal-care. Presented 1 hour prior to

delivery. delivery. Had fetal bradycardia/abruptio.Had fetal bradycardia/abruptio. VentilatedVentilated

CLINICAL CLINICAL FEATURES/COURSEFEATURES/COURSE

IUGR. Microcephaly, Bone age noted to IUGR. Microcephaly, Bone age noted to be advanced.be advanced.

Had persistent tachycardiaHad persistent tachycardia Baby had fluctuating levels of T4 and T3.Baby had fluctuating levels of T4 and T3. Treated with Lugol’s iodine, Inderal and Treated with Lugol’s iodine, Inderal and

PTUPTU

THYROID CHEMISTRYTHYROID CHEMISTRY

20012001 Day 1Day 1 Day 10Day 10 Day 14Day 14

T4T4 0.70.7 >6>6 2.62.6

TSHTSH < 0.1< 0.1 <0.1<0.1 <0.1<0.1

T3T3 264264 570570 8181

COURSE AFTER DISCHARGECOURSE AFTER DISCHARGE

Discharged at 2 m with T4 :0.6 and T3 :69. Discharged at 2 m with T4 :0.6 and T3 :69. Stopped meds prior to discharge.Stopped meds prior to discharge.

Had initially weight loss which later Had initially weight loss which later improved.improved.

At 2 m age had seizures. F/Up thyroid tests At 2 m age had seizures. F/Up thyroid tests were normal.were normal.

Head scan/MRI July 2004 showed non Head scan/MRI July 2004 showed non communicating hydrocephaluscommunicating hydrocephalus

THYROTOXICOSIS IN THYROTOXICOSIS IN NEONATENEONATE

Typically a transient hyperthyroidismTypically a transient hyperthyroidism 1 in 70 Grave’s affected pregnancies.1 in 70 Grave’s affected pregnancies. Mortality :up to 25%Mortality :up to 25%

EtiologyEtiology Placental transfer : Thyroid-stimulating Placental transfer : Thyroid-stimulating

immunoglobulins. Maternal antibodies immunoglobulins. Maternal antibodies wane over 2-3 monthswane over 2-3 months

MATERNAL TBIIMATERNAL TBII

TSH binding inhibiting immunoglobulinTSH binding inhibiting immunoglobulin Levels > 70% predictive neonatal Levels > 70% predictive neonatal

thyrotoxicosis thyrotoxicosis Role of stimulatory and inhibitory Role of stimulatory and inhibitory

immunoglobulinsimmunoglobulins Duration of disease depends on Duration of disease depends on

concentration, degradation rate and concentration, degradation rate and presence or absence of inhibitory Abpresence or absence of inhibitory Ab

BABIES AT RISKBABIES AT RISK

Raised level of TBII in pregnancyRaised level of TBII in pregnancy TBII not assessedTBII not assessed Thyotoxicosis in 3Thyotoxicosis in 3rdrd trimester trimester Thionamide required in 3rd trimesterThionamide required in 3rd trimester Family H/O TSH receptor mutationFamily H/O TSH receptor mutation Evidence of fetal thyrotoxicosisEvidence of fetal thyrotoxicosis

POINTS TO CONSIDERPOINTS TO CONSIDER

Mother with Grave’s disease may not have Mother with Grave’s disease may not have thyrotoxicosis and may be euthyroid or thyrotoxicosis and may be euthyroid or hypothyroid.hypothyroid.

Exposure to anti-thyroid drugs in-utero may delay Exposure to anti-thyroid drugs in-utero may delay symptomssymptoms

Newborn Screening with T4-radioimmune assay, Newborn Screening with T4-radioimmune assay, can detect raised levels of T4can detect raised levels of T4

Positive assay for Thyroid stimulating Positive assay for Thyroid stimulating immunoglobulins….confirmatoryimmunoglobulins….confirmatory

Consider narcotic withdrawalConsider narcotic withdrawal

CLINICAL FEATURES OF CLINICAL FEATURES OF NEONATAL THYROTOXICOSISNEONATAL THYROTOXICOSIS

HyperirritabilityHyperirritability TachycardiaTachycardia GoiterGoiter ExophthalmosExophthalmos LBW and weight lossLBW and weight loss CHFCHF Craniosynostosis/ advanced bone age/microcephaly…Craniosynostosis/ advanced bone age/microcephaly…

psychomotor retardationpsychomotor retardation Jaundice/thrombocytopeniaJaundice/thrombocytopenia

APPROACH TO BABY OF APPROACH TO BABY OF MOTHER WITH GRAVES MOTHER WITH GRAVES

DISEASEDISEASE

Babies at risk

Cord blood fT4,TSH,TSI + examination

If high risk repeat fT4,TSH & examAge 2-7 days

In all babies repeat fT4,TSH and examAge 10-14 days

Hypothyroid. Repeat fT4/TSHTreat with thyroxine if confirmed

HyperthyroidPTU/carbimazole

iodide+/-Propanolol+/-

Normal.No treatment

TREATMENTTREATMENT Should biochemical abnormality in absence Should biochemical abnormality in absence

of symptoms be treated?of symptoms be treated? ThionamidesThionamides block hormone synthesis block hormone synthesis PTUPTU 5-10mg/kg/d in 3 divided doses 5-10mg/kg/d in 3 divided doses CarbimazoleCarbimazole 0.5-1.5mg/kg/d 0.5-1.5mg/kg/d Lugol’s iodineLugol’s iodine (8mg/drop) 1-3 drops/D (8mg/drop) 1-3 drops/D Iopanoic acid/sodium ipodate, Propanolol, Iopanoic acid/sodium ipodate, Propanolol,

Prednisolone–in refractory casesPrednisolone–in refractory cases

TREATMENT TREATMENT (CONTINUED)(CONTINUED)

Exchange transfusions…to reduce TSI Exchange transfusions…to reduce TSI levelslevels

Baby on treatment for thyrotoxicosis is Baby on treatment for thyrotoxicosis is reviewed weekly until stable, then every 2 reviewed weekly until stable, then every 2 weeks and drug dose reduced.weeks and drug dose reduced.

Usually treated for 4-8 weeks.Usually treated for 4-8 weeks. Thyrotoxicosis secondary to mutations of Thyrotoxicosis secondary to mutations of

TSH receptor require ablative treatment TSH receptor require ablative treatment with surgery.with surgery.

SUMMARYSUMMARY Possibility of fetal thyrotoxicosis must be kept Possibility of fetal thyrotoxicosis must be kept

in all mothers with a history of Grave’s disease in all mothers with a history of Grave’s disease regardless of thyroid status/treatment.regardless of thyroid status/treatment.

Thyroid stimulating immunoglobulins (TSI) Thyroid stimulating immunoglobulins (TSI) persist even after thyroid surgery/radioablation persist even after thyroid surgery/radioablation in mother.in mother.

Neonatal thyrotoxicosis secondary to TSIs is a Neonatal thyrotoxicosis secondary to TSIs is a transient disorder, limited by clearance of transient disorder, limited by clearance of maternal antibodiesmaternal antibodies

SUMMARY SUMMARY (CONTINUED)(CONTINUED)

In neonates signs of thyrotoxicosis may be In neonates signs of thyrotoxicosis may be delayed due to effect of maternal anti-delayed due to effect of maternal anti-thyroid drugs or effect of blocking thyroid drugs or effect of blocking antibodies. Cases reported as late as 45 antibodies. Cases reported as late as 45 days.days.

TSH binding inhibitor Ig levels from TSH binding inhibitor Ig levels from mother and from neonate correlate well mother and from neonate correlate well with neonatal thyrotoxicosis.with neonatal thyrotoxicosis.