NEONATAL

GRAVES
DISEASE
Objectives

To present a case of a male neonate born with Neonatal

01 Graves Disease

Discuss Approach on neonates born to mother with

02 Graves Disease

03 Discuss Neonatal Graves Disease

General survey
• BS
• NB
• MALE
• FILIPINO
Chief complaint

Proptosis
History of Present Illness 37 YEARS OLD
G3P2 (2002)
MOTHER

PRENATAL CHECK
UP
-CLAVERIA LHC
-CLAVERIA MOPH

HYPERTHYRODISM
SINCE DECEMBER
2022
POOR COMPLIANCE TO
MAINTENANCE MEDS:
METHIMAZOLE 10MG BID
PROPANOLOL 10MG BID
History of Present Illness PRENATAL LABS
AND ULTRASOUND
DONE
-LOW TSH,
-ELEVATED FT3 AND FT4

SEEN BY OB GYN
AND REFERRED TO
ENT
-SHIFT METHIMAZOLE TO
PTU 20MG BID

REFERRED TO
NMMC OB
History of Present Illness
6 MONTHS AOG

REPEAT THYROID PANEL:

TSH <0.1;
FT3 21.54 pmol/L;
FT4 65.48

REFERRED TO IM
-PTU SHIFTED TO
METHIMAZOLE 10MG
BID
-OTHER SUPPLEMENTS:
FERROUS SULFATE TAB
OD;
CALCIUM CO3 TAB OD
NO OTHER KNOWN
MATERNAL ILLNESSES
History of Present Illness 9 HOURS PRIOR TO
DELIVERY
-ONSET OF LABOR PAIN
-CLAVERIA MOPH:
3CM CERVICAL DILATATION

7 HOURS PRIOR TO
DELIVERY (NMMC
OB ER)
-EPIDURAL ANESTHESIA
DONE

PATIENT WAS
DELIVERED VIA NSD
History of Present Illness
PRETERM 36 WEEKS BY
PHYSICAL MATURITY
BW 2.9 KG, AGA DELIVERED VIA
NORMAL SPONTANEOUS
DELIVERY

LIMP, CYANOTIC, NO CRY

-IMMEDIATE THOROUGH DRYING AND
VIGOROUS STIMULATION
-PPV AND SUCTIONING DONE

GOOD CRY, HR >100, PINK BODY,

FLEXION OF EXTREMITIES ->
HOOKED TO OXYGEN SUPPORT

ADMITTED TO NICU
 PHYSICAL EXAMINATION

AWAKE, NOT IN RESPIRATORY DISTRESS

HEIGHT: 47CM WEIGHT:2.9KG

HC: 31CM CC: 30CM AC: 28CM

VITAL SIGNS:
HR- 158BPM RR- 55CPM T- 36.8’C
O2 sat- 99%
T 1
PHYSICAL EXAMINATION

● HEENT
○ NORMOCEPHALIC, NO FACIAL DYSMORPHISM
○ FLAT, NON BULGING ANTERIOR FONTANELLES 2CMX2CM
○ (+)EXOPTHALMOS, OU; SUBCONJUNCTIVAL HEMORRHAGE, OU; PINK
PALPEBRAL CONJUNCTIVAE
○ NO ALAR FLARING
○ PINK, MOIST LIPS AND ORAL MUCOSA
○ NO LIP AND CLEFT PALATE
○ NO CERVICAL LYMPHADENOPATHIES

● CHEST AND LUNGS

○ SYMMETRICAL CHEST EXPANSION
○ NO RETRACTIONS
○ CLEAR BREATH SOUNDS
PHYSICAL EXAMINATION

● HEENT
○ NORMOCEPHALIC, NO FACIAL DYSMORPHISM
○ FLAT, NON BULGING ANTERIOR FONTANELLES 2CMX2CM
○ (+)EXOPTHALMOS, OU; HYPEREMIC SCLERAE, OU; PINK PALPEBRAL
CONJUNCTIVAE
○ NO ALAR FLARING
○ PINK, MOIST LIPS AND ORAL MUCOSA
○ NO LIP AND CLEFT PALATE
○ NO CERVICAL LYMPHADENOPATHIES

● CHEST AND LUNGS

○ SYMMETRICAL CHEST EXPANSION
○ NO RETRACTIONS
○ CLEAR BREATH SOUNDS
PHYSICAL EXAMINATION

● HEENT
○ NORMOCEPHALIC, NO FACIAL DYSMORPHISM
○ FLAT, NON BULGING ANTERIOR FONTANELLES 2CMX2CM
○ (+)EXOPTHALMOS, OU; HYPEREMIC SCLERAE, OU; PINK PALPEBRAL
CONJUNCTIVAE
○ NO ALAR FLARING
○ PINK, MOIST LIPS AND ORAL MUCOSA
○ NO LIP AND CLEFT PALATE
○ NO CERVICAL LYMPHADENOPATHIES

● CHEST AND LUNGS

○ SYMMETRICAL CHEST EXPANSION
○ NO RETRACTIONS
○ CLEAR BREATH SOUNDS
PHYSICAL EXAMINATION

● CARDIOVASCULAR
○ ADYNAMIC PRECORDIUM
○ PMI AT 5TH LEFT INTERCOSTAL SPACE
○ DISTINCT HEART SOUNDS
○ NO TACHYCARDIA
○ REGULAR RHYTHM
○ NO MURMUR

● ABDOMEN
○ GLOBULAR
○ NORMOACTIVE BOWEL SOUNDS
○ SOFT; NO MASS, NO ORGANOMEGALY
PHYSICAL EXAMINATION

● GENITO-URINARY TRACT
○ GROSSLY MALE
○ NO PENILE DISCHARGES
○ DESCENDED TESTES

● SKIN/EXTREMITIES
○ NO DEFORMITIES
○ HEMATOMA AT NASAL BRIDGE
○ WARM TO TOUCH
○ STRONG PULSES
○ CRT 2 SECONDS
NEURO (-) Atrophy
● Awake, alert (-) Hypotonia
● Cranial nerves:
● 1 – N/A ● MOTOR
● 2 – Isocoric pupils, OU, briskly Spontaneous movement of all extremities
reactive
● 3, 4, 6 – EOM intact ● SENSORY
● 5 – (+) Corneal reflex Moves extremities and cries when touched
● 7 – No facial Asymmetry
● 8 – No hearing loss Primary reflexes:
● 9, 10 – (+) Gag reflex (+)Palmar grasp
● 11 – (+) turn head with resistance (+)Plantar grasp
● 12 - tongue at midline (+)Rooting reflex
(+)Moro reflex
(+)Tonic neck reflex
PRIMARY WORKING
IMPRESSION:

NEONATAL
GRAVES
DISEASE
COURSE IN
THE WARD
APPROACH TO NEONATES BORN TO MOTHERS
WITH GRAVES DISEASE
 HOSPITAL DAY 1
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • Routine newborn care
(-) TACHYPNEA distress Disease • Credes prophylaxis OU
• Vitamin K 1mg IM
(-) JITTERNESS HR 156 • Hepatitis B 0.5ml IM
(-) SEIZURES RR 50s • BCG 0.05ml ID
(-) POOR SUCK T 36.8-37.3
Preductal O2 sat 98% Labs:
Postductal O2 sat 97% • For TSH, FT3 and FT4 at 72 hours of
(+) Exopthalmos, OU life
(+) Subconjunctival • For NBST and Hearing screening
hemorrhage, OU after 24 hours of life
(-) Alar flaring • For CCHD screening
(-) Retractions
(-) Arrhythmia • Breastfeeding with mother
APPROACH TO NEONATES BORN TO MOTHERS
WITH GRAVES DISEASE
 HOSPITAL DAY 2-3
PROBLEM LIST: PROPTOSIS; FAST BREATHING
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves Labs:
(+) TACHYPNEA distress Disease; • For TSH, FT3 and FT4 at 72 hours of
life
HR 150-160 T/C Neonatal • For CBC, CRP
RR 55-60 pneumonia • For Chest xray APL
T 36.8-37.3
O2 sat 90% at room air Meds:
(+) Exopthalmos, OU • Ampicillin 50mkd q 12H
(+) Subconjunctival • Gentamicin 4mkd q 24H
hemorrhage, OU • Hooked to oxygen support at 2lpm
(-) Alar flaring via nasal cannula
(+)Subcostal Retractions CBC
Clear breath sounds WBC 14.66
(-) Murmur HGB 19.1
HCT 58.0
NEU 48.3
LYM 32.8
MON 17.3
EOS 0.8
PLATELET CT 218

CRP 14.8
 HOSPITAL DAY 2-3
PROBLEM LIST: PROPTOSIS; FAST BREATHING
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves Labs:
(+) TACHYPNEA distress Disease; • For TSH, FT3 and FT4 at 72 hours of
life
(-) JITTERNESS HR 150-160 T/C Neonatal • For CBC, CRP
(-) SEIZURES RR 55-60 pneumonia • For Chest xray APL
(-) POOR SUCK T 36.8-37.3
Preductal O2 sat 98% Meds:
Postductal O2 sat 97% • Ampicillin 50mkd q 12H
(+) Exopthalmos, OU • Gentamicin 4mkd q 24H
(+) Subconjunctival • Hooked to oxygen support at 2lpm
hyperemia, OU via nasal cannula
(-) Alar flaring
(-) Retractions CBC
(-) Murmur WBC 14.66
HGB 19.1
HCT 58.0
NEU 48.3
LYM 32.8
MON 17.3
EOS 0.8
PLATELET CT 218
 HOSPITAL DAY 4-6
PROBLEM LIST: PROPTOSIS; FAST BREATHING
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • Insert OGT
(+) TACHYPNEA distress Disease; • Start OGT feeding with expressed
breastmilk
(+) TACHYCARDIA HR 160-170BPM Neonatal • For ECG and Repeat chest xray APL
(-) JITTERNESS RR 60CPM pneumonia - • For CBC, Blood CS
(-) SEIZURES T 36.8 Worsening
O2 sat 97% at 2LPM • Start:
(+) Exopthalmos, OU Methimazole 0.4mg/pptab BID (0.27mkD)
(+) Subconjunctival hyperemia, OU Propanolol 1.9mg/pptab TID (2mkD)
(-) Alar flaring • Shift Ampicillin to Piperacillin +
(+) SC Retractions, clear breath Tazobactam at 100mkd q 8H
sounds • Oxygen support at 1LPM via NC
• Refer to Ophtha for further evaluation
CBC THYROID PANEL
WBC 13.01
HGB 18.2 TSH (0.3 - 4.2 <0.1
mIU/L)
HCT 57.3 FT3 (2.8 - 7.1 19.83
NEU 36.2 pmol/L)
LYM 44.4 FT4 (12 - 22 46.08
pmol/L)
MON 17.9
EOS 1.1
PLATELET CT 202
 HOSPITAL DAY 4-6
PROBLEM LIST: PROPTOSIS; FAST BREATHING
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • Insert OGT
(+) TACHYPNEA distress Disease; • Start OGT feeding with expressed
breastmilk
(+) TACHYCARDIA HR 160-170BPM Neonatal • For ECG and Repeat chest xray APL
(-) JITTERNESS RR 60CPM pneumonia • For CBC
(-) SEIZURES T 36.8
(-) POOR SUCK Preductal O2 sat • Start:
Postductal O2 sat Methimazole 0.4mg/pptab BID (0.27mkD)
(+) Exopthalmos, OU Propanolol 1.9mg/pptab TID (2mkD)
(+) Subconjunctival hyperemia, OU • Shift Ampicillin to Piperacillin +
(-) Alar flaring Tazobactam at 100mkd q 8H
(+) SC Retractions, clear breath • Oxygen support at 1LPM via NC
sounds • Refer to Ophtha for further evaluation
CBC THYROID PANEL 4th DOL
WBC 13.01
HGB 18.2 TSH (0.3 - 4.2 <0.1
mIU/L)
HCT 57.3 FT3 (2.8 - 7.1 19.83
NEU 36.2 pmol/L)
LYM 44.4 FT4 (12 - 22 46.08
pmol/L)
MON 17.9
EOS 1.1 CRP 14.8
PLATELET CT 202
 APPROACH TO NEONATES BORN TO MOTHERS
WITH GRAVES DISEASE

Patient B.S.
THYROID 4th DOL
PANEL
TSH <0.1
FT3 19.83
FT4 46.08
 HOSPITAL DAY 7-8
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • For repeat TSH, FT3, FT4 after 2nd
(-) JITTERNESS distress Disease; week of life
• Continue meds:
(-) SEIZURES HR 140-150s Neonatal
-Methimazole
GOOD SUCK RR 40s pneumonia - -Propanolol
GOOD ACTIVITY T 36.8 Resolving -Piperacillin + Tazobactam
O2 sat 99% at 0.5-1LPM -Gentamicin
(+) Exopthalmos, OU • Tapering of oxygen support
(+) Subconjunctival
hyperemia, OU • Seen by Ophtha:
(-) Alar flaring Dx: Subconjunctival hemorrhage, OU
(-) Retractions No active management
(-) Murmur

Blood CS: (+)MRSA

(incubated after 2 days)
 HOSPITAL DAY 9-10
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • For TRAb
distress Disease; • Continue meds:
-Methimazole
HR 140 BPM Neonatal
-Propanolol
RR 44 CPM pneumonia - Completion of antibiotics:
T 36.5-37’C Resolving -Piperacillin + Tazobactam
O2 sat 98% at room air -Gentamicin
(+) Exopthalmos, OU • D/C Oxygen support
(+) Subconjunctival
hyperemia, OU • Re-evaluated by Ophtha:
(-) Alar flaring Dx: Consider Transient thyroid
(-) Retractions orbitopathy, OU
(-) Murmur No active management
 HOSPITAL DAY 11-16
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves • Breastfeeding per demand
(-) TACHYPNEA distress Disease; • Continue meds:
-Methimazole
(-) TACHYCARDIA HR 140s Neonatal
-Propanolol
(-) JITTERNESS RR 40-50s pneumonia - Completion of antibiotics:
(-) SEIZURES T 36.8 Resolving -Piperacillin + Tazobactam
GOOD SUCK AND O2 sat 97%
ACTIVITY (+) Exopthalmos, OU • For repeat TSH, FT3, FT4
(-) Alar flaring
(-) Retractions
(-) Murmur

TSH 33.65 IU/L

Receptor Ab
Reference: <1.75
 HOSPITAL DAY 11-16
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves For TRAb
(+) TACHYPNEA distress Disease; • Continue meds:
-Methimazole
(+) TACHYCARDIA HR 160-170BPM Neonatal
-Propanolol
(-) JITTERNESS RR 60CPM pneumonia - Completion of antibiotics:
(-) SEIZURES T 36.8 Resolving -Piperacillin + Tazobactam
(-) POOR SUCK Preductal O2 sat -Gentamicin
Postductal O2 sat • D/C Oxygen support
(+) Exopthalmos, OU
(+) Subconjunctival • Re-evaluated by Ophtha:
hyperemia, OU Dx: Consider Transient thyroid
(-) Alar flaring orbitopathy, OU
(-) Retractions No active management
(-) Murmur

TSH 33.65 IU/L

Receptor Ab
Reference: <1.75
 HOSPITAL DAY 17-20
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, comfortable Neonatal Graves • Breastfeeding per demand
(+) TACHYPNEA HR 140s Disease- • Continue meds:
-Methimazole
(+) TACHYCARDIA RR 40-50s Resolving;
-Propanolol
(-) JITTERNESS T 36.8 Neonatal -D/C Piperacillin + Tazobactam
(-) SEIZURES O2 sat 97% pneumonia -
(-) POOR SUCK (+) Exopthalmos, OU Resolved -For prebilling
(-) Alar flaring -For repeat thyroid function test after 2
(-) Retractions weeks to 1 month
-Avoid inducing hypothyroidism
(-) Murmur

THYROID PANEL
TSH (0.25-5.0pmol/l) 0.16
FT3 (3.8-8.5pmol/l) 10.01
FT4 (10.3-22.8pmol/l) 30.75
 HOSPITAL DAY 17-20
PROBLEM LIST: PROPTOSIS
S O A P
(+) PROPTOSIS Awake, not in respiratory Neonatal Graves For TRAb
(+) TACHYPNEA distress Disease; • Continue meds:
-Methimazole
(+) TACHYCARDIA HR 160-170BPM Neonatal
-Propanolol
(-) JITTERNESS RR 60CPM pneumonia - Completion of antibiotics:
(-) SEIZURES T 36.8 Resolving -Piperacillin + Tazobactam
(-) POOR SUCK Preductal O2 sat -Gentamicin
Postductal O2 sat • D/C Oxygen support
(+) Exopthalmos, OU
(+) Subconjunctival • Re-evaluated by Ophtha:
hyperemia, OU Dx: Consider Transient thyroid
(-) Alar flaring orbitopathy, OU
(-) Retractions No active management
(-) Murmur

THYROID PANEL
TSH (0.25-5.0pmol/l) 0.16
FT3 (3.8-8.5pmol/l) 10.01
FT4 (10.3-22.8pmol/l) 30.75
FINAL DIAGNOSIS
NEONATAL GRAVES DISEASE;
NEONATAL PNEUMONIA;
PRETERM, 36 WEEKS BY
PHYSICAL MATURITY, BW 2.9KG,
APPROPRIATE FOR GESTATIONAL
AGE, CEPHALIC, LIVE MALE
NEONATE, APGAR SCORE 3, 6, 8;
MATERNAL FACTOR:
HYPERTHYROIDISM
º CASE DISCUSSION
NEONATAL GRAVES DISEASE
● THERE IS ELEVATION OF THYROID HORMONE (T3 AND
T4)
● DEVELOPS IN 1 TO 5 % OF INFANTS BORN TO MOTHERS
WITH GRAVES DISEASE
● CAUSED BY TRANSPLACENTAL PASSAGE OF MATERNAL
STIMULATORY THYROTROPIN RECEPTOR ANTIBODIES.
HYPOTHALAMUS-
PITUITARY-
THYROID AXIS
PATHOPHYSIOLOGY
CLINICAL MANIFESTATIONSIrritability
Low birthweight Stare Hyperactivity
(IUGR) Exophthalmos Restlessness
Premature birth
Poor sleep
Poor weight gain

Microcephalic
Tachycardia Frontal bossing
Arrhythmias Triangular facies
Cardiomegaly
Bounding pulses Hyperphagia

Diffuse goiter Warm, moist skin

MONITORING DURING PREGNANCY
● Maternal serum TSHR-Ab
-Measurement during third trimester
-Helps estimate the risk of neonatal Graves disease

● Fetal hyperthyroidism
-Monitor symptoms of fetal hyperthyroidism (fetal hyperactivity,
tachycardia, advance bone maturation, goiter)
DIAGNOSIS
● LOW THYROID-STIMULATING
HORMONE (TSH)
● ELEVATED FREE THYROXINE (FT4)
AND TOTAL TRIIODOTHYRONINE (T3)
● TSH RECEPTOR AUTOANTIBODIES
● THYROID ULTRASOUND

Patient B.S.
THYROID
PANEL
TSH <0.1
FT3 19.83
FT4 46.08
 APPROACH TO NEONATES BORN TO MOTHERS
WITH GRAVES DISEASE

Patient B.S.
THYROID 4th DOL
PANEL
TSH <0.1
FT3 19.83
FT4 46.08
MANAGEMENT
METHIMAZOLE AND BETA ADRENERGIC BLOCKER

● METHIMAZOLE
(0.25 to 1.0 mg/kg/day)
-Anti-thyroid drugs

● PROPANOLOL
(2 mg/kg/day every eight hours)
-Beta adrenergic blocker
-an important adjunct in controlling neuromuscular and
cardiovascular hyperactivity.
- inhibits T4 conversion to T3
MANAGEMENT
● IODINE
-inhibit thyroid hormone release
-given 1 to 2 weeks
-Lugol's solution (126 mg iodine/mL), 1 drop (8mg) PO every 8
hours, or
-Potassium iodide solution 1 to 2 drops OD

● OTHERS:
● Glucocorticoids
- inhibit thyroid hormone secretion and decrease peripheral
conversion of T4 to T3
● Digoxin
-helpful if heartfailure is present
MANAGEMENT

● Neonatal Graves Hyperthyroidism usually resolves

spontaneously between 3 and 12 weeks of life but can
persist for 6 months or longer.

● Treatment should be gradually decreased then

discontinued

● Frequent thyroid function tests monitoring

PROGNOSIS
● Rapid improvement in most neonates with prompt and adequate therapy

● Growth retardation, craniosynostosis, hyperactivity, and developmental and behavioral

problems have been described as long-term sequelae of neonatal Graves
hyperthyroidism

● Some infants with neonatal graves hyperthyroidism later have diminished TSH
secretion, resulting in central hypothyroidism
Thank you

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REFERENCES
● Segni M. Neonatal Hyperthyroidism. [Updated 2019 Apr 15]. In: Feingold KR, Anawalt B, Blackman MR,
et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from:
https://www.ncbi.nlm.nih.gov/books/NBK279019/
● https://www.uptodate.com/contents/evaluation-and-management-of-neonatal-graves-disease/abstract/3
● Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus
JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the
Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid. 2017
Mar;27(3):315-389. doi: 10.1089/thy.2016.0457. Erratum in: Thyroid. 2017 Sep;27(9):1212. PMID:
28056690.
● Gomella, T., & Cunningham, M. (2013). Neonatology 7th Edition. McGraw-Hill Prof Med/Tech.