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NEONATE BORN TO MOTHER WITH GRAVE’S DISEASE Baby boy born at 24 weeks gestation, weight 559G Mother 25year,G6 P4 Ab1 LC4. Known case of Grave’s disease, with uncontrolled thyrotoxicosis since 1999…non compliant on treatment (PTU/Inderal). No PNC. With pre-eclampsia, abruption- severe decelerations-Emergency C-section. NICU COURSE Maternal TSI on Sept 2003: 212% (Normal 0 - 129%) • Resuscitated at birth Apgars 3,6 & 8.Ventilated ….given curosurf and transferred to ICN on portable ventilator • On exam, baby 24 weeks gestation AGA Systemic exam WNL. No evidence of goiter/exophthalmos. Initially had heart rates in 160-170 but later normalized. MANAGEMENT IN NICU Hypoperfusion/hypotension/metabolic acidosis needing NS bolus x 2 and inotrope support. D2-3 echo showed PDA…treated with Indomethacin Head sono…no IVH. Drug screen normal THYROID CHEMISTRIES Infant values Day -1 Day -7 T4,free (0.6-1.70) TSH (0.4-5) T3,total (70-204) 1.26 0.45 0.07 0.01 124 97 PRESENT CONDITION Presently baby on IMV, being treated for evolving lung disease…diuretics and steroid nebulization On TPN and NG feeds. OBSTETRIC HISTORY 7/96 40wks 9/97 40wks 11/01 31wks 9/03 36wks 12/00 15wks 7/04 24wks 9lbs NSVD 7lbs NSVD 2lbs NSVD 3lbs NSVD miscarriage 1.2lbs CS Dallas Mexico Thomason Thomason Thomason BABY WITH NEONATAL THYROTOXICOSIS Baby No.3 was born at Thomason in 2001 Preterm 31 wks SGA , BW:1130 G No prenatal-care. Presented 1 hour prior to delivery. Had fetal bradycardia/abruptio. Ventilated CLINICAL FEATURES/COURSE IUGR. Microcephaly, Bone age noted to be advanced. Had persistent tachycardia Baby had fluctuating levels of T4 and T3. Treated with Lugol’s iodine, Inderal and PTU THYROID CHEMISTRY 2001 Day 1 Day 10 Day 14 T4 >6 2.6 TSH < 0.1 <0.1 <0.1 T3 570 81 0.7 264 COURSE AFTER DISCHARGE Discharged at 2 m with T4 :0.6 and T3 :69. Stopped meds prior to discharge. Had initially weight loss which later improved. At 2 m age had seizures. F/Up thyroid tests were normal. Head scan/MRI July 2004 showed non communicating hydrocephalus THYROTOXICOSIS IN NEONATE Typically a transient hyperthyroidism 1 in 70 Grave’s affected pregnancies. Mortality :up to 25% Etiology Placental transfer : Thyroid-stimulating immunoglobulins. Maternal antibodies wane over 2-3 months MATERNAL TBII TSH binding inhibiting immunoglobulin Levels > 70% predictive neonatal thyrotoxicosis Role of stimulatory and inhibitory immunoglobulins Duration of disease depends on concentration, degradation rate and presence or absence of inhibitory Ab BABIES AT RISK Raised level of TBII in pregnancy TBII not assessed Thyotoxicosis in 3rd trimester Thionamide required in 3rd trimester Family H/O TSH receptor mutation Evidence of fetal thyrotoxicosis POINTS TO CONSIDER Mother with Grave’s disease may not have thyrotoxicosis and may be euthyroid or hypothyroid. Exposure to anti-thyroid drugs in-utero may delay symptoms Newborn Screening with T4-radioimmune assay, can detect raised levels of T4 Positive assay for Thyroid stimulating immunoglobulins….confirmatory Consider narcotic withdrawal CLINICAL FEATURES OF NEONATAL THYROTOXICOSIS Hyperirritability Tachycardia Goiter Exophthalmos LBW and weight loss CHF Craniosynostosis/ advanced bone age/microcephaly…psychomotor retardation Jaundice/thrombocytopenia APPROACH TO BABY OF MOTHER WITH GRAVES DISEASE Babies at risk Cord blood fT4,TSH,TSI + examination If high risk repeat fT4,TSH & exam Age 2-7 days In all babies repeat fT4,TSH and exam Age 10-14 days Hypothyroid. Repeat fT4/TSH Treat with thyroxine if confirmed Hyperthyroid PTU/carbimazole iodide+/Propanolol+/Normal.No treatment TREATMENT Should biochemical abnormality in absence of symptoms be treated? Thionamides block hormone synthesis PTU 5-10mg/kg/d in 3 divided doses Carbimazole 0.5-1.5mg/kg/d Lugol’s iodine (8mg/drop) 1-3 drops/D Iopanoic acid/sodium ipodate, Propanolol, Prednisolone–in refractory cases TREATMENT (CONTINUED) Exchange transfusions…to reduce TSI levels Baby on treatment for thyrotoxicosis is reviewed weekly until stable, then every 2 weeks and drug dose reduced. Usually treated for 4-8 weeks. Thyrotoxicosis secondary to mutations of TSH receptor require ablative treatment with surgery. SUMMARY Possibility of fetal thyrotoxicosis must be kept in all mothers with a history of Grave’s disease regardless of thyroid status/treatment. Thyroid stimulating immunoglobulins (TSI) persist even after thyroid surgery/radioablation in mother. Neonatal thyrotoxicosis secondary to TSIs is a transient disorder, limited by clearance of maternal antibodies SUMMARY (CONTINUED) In neonates signs of thyrotoxicosis may be delayed due to effect of maternal antithyroid drugs or effect of blocking antibodies. Cases reported as late as 45 days. TSH binding inhibitor Ig levels from mother and from neonate correlate well with neonatal thyrotoxicosis.