Neonatal

Hyperthyroidism
Demography
Baby P,
36 weeks, male child
Born on 17/11/22, by LSCS
Birth weight - 2660 grams, AGA
Born to G7 With no living issues
Had previous 1 abortion and 4 perinatal deaths and 1 IUFD
(Non immune hydrops)
Mother medical history
Diagnosed case of graves, since 2015 with maternal TRAb-
40 and Hyperprolactinemia

Mother was on methimazole, thyroxine, Bromocriptine

Obstetric history
A1 – Spontaneous abortion at 2 months
P1 - Term, NVD, male child, expired at 1 hour of life
P2- 7 months, NVD, female child, expired at day 4 of life. ?
Aspiration
P3- 7 months, emergency LSCS in view of MSL, female child
expired on day 2
P4 -7 months, NVD, non immune hydrops, male child, IUFD
P5- 7 months, LSCS, male child expired on day 3
Antenatal history
Level 2 USG was normal, USG done at 28 weeks, s/o mildly
enlarged thyroid gland,
Followed which foetal MRI was done - s/o foetal
thyromegaly

Last TFT of mother

TSH 0.08 (0.4-4mU/L)
T3 2.27 (0.8-2 ng/dl)
T4 20.8(4.8-12.7mcg/dl)
Birth and postnatal course
Delivered by elective LSCS, CIAB Apgar was 8 and 9
Liquor was clear.
Started on exclusive breast feeding

Child had Jitteriness and intermittent tachycardia, tachypnea,

bounding pulses, dry skin
AF was 1 X 1 cm
Diffuse goitre palpable 2*2cm
Eye signs - the baby was noted to have Intermittent upper
eyelid retraction of both eyes
Continued
Possibilty of neonatal graves was considered, and
workup was sent
And it was confirmed biochemically,

18/11/22
TSH 0.005(0.27-4.2 micro IU/ml)
T4 19.4(4.8-12.7mcg/dl)
T3 0.992 (0.8-2 ng/dl)
TPO 77.3 (034 IU/ml)
TRAb 40
Approach to case of neonatal
hyperthyroidism
Prevalence of GD in pregnant women: 0.1 to 0.4%
Hyperthyroidism develops in babies born to mothers with
the most potent stimulatory activity in serum.
This corresponds to 1-2% of mothers with Graves’ disease,
or 1 in 50,000 newborns, an incidence that is approximately
four times higher than is that for transient neonatal
hypothyroidism due to maternal TSH receptor blocking
antibodies.
Causes of neonatal
hyperthyroidism:
Autoimmune hyperthyroidism (neonatal GD)
Transplacental passage of TRAb from mother to foetus
Transient (generally resolves in 4–5 months after TRAb
clearance)

Nonautoimmune hyperthyroidism Activating

mutation in the TSH receptor (autosomal dominant)

Activating mutation in GNAS (McCune-Albright

syndrome) Permanent (persists after the neonatal
period.
Other causes
Use of high dose of thyroxine in treatment of congenital
hypothyroidism ( FT4 to be maintained at upper half of
normal)

Iodine induced Hyperthyroidism

Pathophysiology
Mothers of graves have 2 types of TRAb:

Stimulating antibodies cause hyperthyroidism

Blocking antibodies cause hypothyroidism

Antibodies may persist after thyroid ablation by surgery/RAI

Continued
Belongs to Ig G Class, hence freely cross the placenta

Fetal TSHR starts responding from 2nd trimester

Sometimes both types of antibodies are present, thyroid

status depend on balance between these antibodies, and
antithyroid drugs, mother taking
Clinical features-Foetal hyperthyroidism

Tachycardia
Goitre
Intrauterine growth retardation
Oligohydramnios
Advanced bone maturation
Prematurity
Foetal death
Polyhydramnios is typically associated with a goiter with resultant
esophageal and/or tracheal obstruction.
Hydrops
 Clinical features
Neonatal hyperthyroidism:
Hemodynamic instability (tachycardia, SVT, hypertension,
tachypnoea/respiratory distress, hyperthermia)

Irritability, sleep difficulty, hyperexcitability

Increased appetite, feeding difficulties Poor weight gain or

weight loss
Continued
Diarrhoea Flushing/sweating Stare and/or eyelid
retardation

Small fontanelle , Craniosynostosis, microcephaly

Severe cases: hepatosplenomegaly, thrombocytopenia,

jaundice, pulmonary hypertension, cardiac failure, death.
Neonatal screening
High risk neonates:
Positive or unknown maternal TRAB between 20 to 24 weeks
in setting of maternal graves
Fetal signs of hyperthyroidism
Family history of activating mutation in TSH receptor

LOW RISK:
Negative maternal TRAb between 20 to 24 weeks in setting of
graves---- no specific follow up needed
Continued
Determine TRAb in cord blood if assay available

Day 1:History and examination, TRAb if cord assay not done

Day 3 to 5:TSH and FT4 to be sent when biochemical
hyperthyroidism typically develop, if values are within normal
limits screened again on, Day 10-14: TSH, FT4

Onset of hyperthyroidism can be delayed up to 10 to 14 days

due to the presence of blocking antibodies or maternal
antithyroid drugs ( methimazole- 36 to 72 hrs)
Continued
If no abnormalities are identified after 2 weeks of life,
routine testing can be discontinued.

At 4 weeks of life and again at 2 and 3 months of life, infants

should be assessed clinically to identify the small population
of infants with delayed presentation
Management
Treatment duration
Neonatal hyperthyroidism due to maternal GD is self-limited
Duration determined by the rate of disappearance of
maternal TRAb from the infant circulation. TRAb half-lives
have been reported to be approximately 12 days.
Depending on the initial TRAb level, neonatal GD generally
resolves by 6 months, instances of persistence to 12
months has been reported
Treatment duration is most commonly 1 to 2 months.
MMI dose should be decreased and eventually discontinued
when fT4 levels are within the reference range.
Management in index case
Childs was started on methimazole at 0.5mg/kg/day and
propanol at 1mg/kg/day , after which tachypnoea and
tachycardia settled.
TFT repeated
2/12/22
TSH 0.005(0.27-4.2 micro IU/ml)

T4 10.9(4.8-12.7mcg/dl)
T3 2.11(0.8-2 ng/dl)
Continued
Child was monitored closely for tachycardia, tachypnea,
irritability, loose stools, hyperthermia, diaphoresis
No features of cardiac failure, cranial synostosis.
ECG
Follow up
During the follow up as child has became asymptomatic propranolol
was stopped on 5th December 2022
On 19th December methimazole dose was reduced to 0.25mg/kg/day

18/12/22 31/12/22
TSH 0.04(0.27-4.2 micro 0.01(0.27-4.2 micro
IU/ml) IU/ml)
T3 1.94(0.8-2 ng/dl) 2.28(0.8-2 ng/dl)
T4 6.49(4.8-12.7mcg/dl) 10.57(4.8-12.7mcg/dl)
Long term complications

Apart from short term consequences long term

complication with histories of neonatal thyrotoxicosis can
have intellectual impairment and craniosynostosis in some
cases.
Maintaining Euthyroid status in hyperthyroid pregnant and
close follow up of the child after birth has to be done.
Reference
van der Kaay DC, Wasserman JD, Palmert MR. Management of
Neonates Born to Mothers With Graves’ Disease. Pediatrics.
2016;137(4):e20151878
Kurtoğlu S, Özdemir A. Fetal neonatal hyperthyroidism: diagnostic and
therapeutic approachment. Turk Pediatri Ars. 2017 Mar 1;52(1):1-9. doi:
10.5152/TurkPediatriArs.2017.2513. PMID: 28439194; PMCID:
PMC5396815
Segni M. Neonatal Hyperthyroidism. [Updated 2019 Apr 15]. In:
Feingold KR, Anawalt B, Blackman MR, et al., editors. Endotext