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Maternal Iodine Exposure: A Case of
Fetal Goiter and Neonatal Hearing Loss
Rachael T. Overcash, MD, MPH,a,b Krishelle L. Marc-Aurele, MD,c Andrew D. Hull, MD,a Gladys A. Ramos, MDa
A 27-year-old gravid 1 at 27 weeks 6 days with a history of
hypothyroidism had an ultrasound that demonstrated a 3.9 × 3.2 × 3.3cm well-circumscribed anterior neck mass, an extended fetal head, and
polyhydramnios. Further characterization by magnetic resonance imaging
(MRI) showed a fetal goiter. During her evaluation for the underlying cause
of the fetal goiter, the patient revealed she was taking nutritional iodine
supplements for treatment of her hypothyroidism. She was ingesting 62.5
times the recommended amount of daily iodine in pregnancy. The excessive
iodine consumption caused suppression of the fetal thyroid hormone
production, resulting in hypothyroidism and goiter formation. After the
iodine supplement was discontinued, the fetal goiter decreased in size. At
delivery, the airway was not compromised. The infant was found to have
reversible hypothyroidism and bilateral hearing loss postnatally. This
case illustrates the importance of examining for iatrogenic causes for fetal
anomalies, especially in unregulated nutritional supplements.
Fetal goiter is a rare condition. It is
commonly due to maternal thyroidstimulating antibodies crossing the
placenta and stimulating the fetal
thyroid tissue or due to inborn
dyshormonogenesis errors in thyroid
hormone synthesis.1 A fetal goiter can
be diagnosed prenatally on ultrasound
as a homogeneous anterior neck mass.
When the goiter is large, it can affect
the neonatal airway at delivery.
Iodine is required for thyroid
hormone synthesis. After
consumption, iodine is converted to
iodide and absorbed by the thyroid
gland. Iodine is most commonly
found in food. It is also in cough
syrups (potassium iodide), vitamins,
amiodarone, antiseptic solutions,
and radiologic contrast.2 Although
iodine consumption is important
for adequate thyroid function,
excessive iodine consumption can
lead to inhibition of thyroid hormone
synthesis, resulting in hypothyroidism
and goiter formation. We present a
PEDIATRICS Volume 137, number 4, April 2016:e20153722
case of an iodine-induced fetal goiter
diagnosed at 27 weeks gestation
in a patient consuming excessive
iodine supplements for treatment of
hypothyroidism.
CASE
At 27 weeks and 6 days of gestation,
a 27-year-old primigravida woman
presented for a growth ultrasound
that showed an appropriately
grown fetus with a 3.9 × 3.2 × 3.3cm homogeneous, mildly echogenic,
well-circumscribed neck mass (Fig
1). The mass had vascular flow on
color Doppler and surrounded the
trachea. Due to the anterior position
of the mass, the fetus was in a brow
presentation and appeared to be “stargazing,” with the neck hyperextended.
There was also polyhydramnios with
an amniotic fluid index of 30.1 cm
(normal: 5–25 cm). The fetal heart
rate was 132 beats per minute. There
were no other fetal abnormalities
abstract
aDivision
of Maternal-Fetal Medicine, Department of
Reproductive Medicine, and cDivision of Neonatology,
Department of Pediatrics, University of California San
Diego, San Diego, California; and bDivision of MaternalFetal Medicine, Department of Obstetrics and Gynecology,
MedStar Washington Hospital Center, Washington, District
of Columbia
Dr Overcash was involved in the care of the patient,
conceptualized and drafted the initial manuscript
and literature review, and submitted final
manuscript; Dr Marc-Aurele was involved in the
care of the neonate, and conceptualized and edited
the manuscript; Drs Hull and Ramos were involved
in the care of the patient, and conceptualized and
edited the manuscript; and all authors approved
the final manuscript as submitted and agree to be
accountable for all the aspects of the work.
DOI: 10.1542/peds.2015-3722
Accepted for publication Jan 22, 2016
Address correspondence to Rachael T. Overcash,
MD, MPH, Division of Maternal-Fetal Medicine,
Department of Obstetrics and Gynecology, MedStar
Washington Hospital Center, 106 Irving St, NW, POB
108 South, Washington, DC 20010. E-mail: rachael.
[email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
1098-4275).
Copyright © 2016 by the American Academy of
Pediatrics
FINANCIAL DISCLOSURE: The authors have
indicated they have no financial relationships
relevant to this article to disclose.
FUNDING: No external funding.
POTENTIAL CONFLICT OF INTEREST: The authors
have indicated they have no potential conflicts of
interest to disclose.
To cite: Overcash RT, Marc-Aurele KL, Hull AD,
et al. Maternal Iodine Exposure: A Case of Fetal
Goiter and Neonatal Hearing Loss. Pediatrics.
2016;137(4):e20153722
CASE REPORT
identified. The differential diagnosis
for these ultrasound findings
included a teratoma, lymphangioma,
goiter, branchial cleft cyst, and
vascular malformation such as
hemangioma.
FIGURE 1
Axial view of the anterior neck mass measuring 3.9 × 3.2 × 3.3 cm (black arrow) with trachea (white
arrow) in the center at 27 weeks 6 days of gestation.
The patient’s pregnancy was
complicated by hypothyroidism. She
was taking Armour Thyroid, a
natural thyroid hormone, which is
quivalent of 38 μg thyroxine (T4).
After the diagnosis of the fetal neck
mass, maternal thyroid function
was assessed. Her thyrotropin (TSH)
was 2.73 μIU/mL (normal: 0.4–3.6
μIU/mL), total T4 was 8.3 μg/dL
(normal: 7.5–10.3 μg/dL), free T4
was 0.67 ng/dL (normal: 0.6–1.0 ng/
dL), and total triiodothyronine was
2.0 ng/mL (1.8–3.7 ng/mL). She was
also negative for thyroid-stimulating
immunoglobulins, thyroid peroxidase
antibodies, and thyroglobulin
antibodies.
The patient underwent a fetal MRI
to better characterize the neck mass.
On MRI at 29 weeks gestation, the
mass measured 3.4 × 2.2 cm with
the morphologic appearance of an
enlarged thyroid gland, consistent
with a fetal goiter (Fig 2). The trachea
was surrounded by the mass but
appeared patent.
Upon further questioning of the
patient, we discovered that as part
of her hypothyroid treatment by
a naturopathic provider, she was
taking 2 pills per day of Iodizyme-HP
dietary supplement (2.5 mg iodine
and 3.75 mg iodide = 6.25 mg total
in each pill). Her supplemental
iodine and natural thyroid hormone
replacement were immediately
discontinued. She was placed on
Synthyroid 75 μg daily instead.
FIGURE 2
Sagittal view of fetal goiter (black arrow) on MRI (fiesta steady state free precession) at 29 weeks’
gestation.
e2
Given the ultrasound and MRI
findings, there was concern about
airway patency at delivery. A
multidisciplinary team was formed
involving perinatology, neonatology,
pediatric anesthesiology, and
pediatric otolaryngology. An ex
utero intrapartum treatment (EXIT)
OVERCASH et al
procedure was planned for delivery
to allow for appropriate management
of the neonatal airway.
One month after discontinuing
the supplemental iodine, the fetal
goiter decreased in size to 2.7 × 2.4 ×
2.3 cm. The fetal neck was less
extended and the polyhydramnios
resolved (Fig 3). A follow-up
MRI also showed the mass was
smaller (1.5 × 2.1 cm) with a patent
trachea. The multidisciplinary
team reviewed these findings and
agreed to proceed with a primary
cesarean delivery scheduled with the
pediatric anesthesiologist, pediatric
otolaryngologist, and neonatologist
in attendance to manage a potentially
difficult airway but without a planned
EXIT procedure.
At 39 weeks gestation, the patient
presented for a primary cesarean
delivery. A male infant weighing
3230 g with Apgar score of 8 at
1 minute and 9 at 5 minutes was
delivered with some degree of
difficulty given the fetal head
position. The infant cried at time of
delivery. Pediatric anesthesiology,
pediatric otolaryngology, and
neonatology evaluated the neonate.
At birth, there was no airway
compromise and only blow by oxygen
was required. On examination,
no neck mass was visualized or
palpated but the neonate was noted
to maintain his head to the left due
to in utero positioning. The infant at
birth was 30th percentile for weight,
71st percentile for length, and 54th
percentile for head circumference. At
8 hours of life, the infant developed
respiratory distress, requiring
intubation for surfactant. The
neonatology team intubated him
without difficulty on the first attempt
and extubated him the next day.
Serial thyroid function testing
during the 8-day hospitalization was
normal without any intervention.
Just after delivery, the infant’s TSH
was 22.6 μIU/mL (normal 0–3
days old: 5.17–14.6 μIU/mL) and
free T4 was 1.9 ng/dL (normal 0–3
PEDIATRICS Volume 137, number 4, April 2016
FIGURE 3
Axial view of the fetal goiter showing a decrease in size measuring 2.7 × 2.4 cm (black arrow) with a
patent trachea (white arrow) at 38 weeks gestation.
days old: 0.66–2.71 ng/dL).3 His
TSH and free T4 decreased over
his hospital course. On day of life
(DOL) 2, the TSH was 5.97 μIU/mL
and the free T4 was 2.65 ng/dL. On
DOL 6, the TSH was 1.53 μIU/mL
(normal 4–30 days old: 0.43-16.1
μIU/mL) and free T4 was 2.58 ng/dL
(normal 4–30 days old: 0.83–3.09
ng/dL).3 A neck ultrasound showed
a diffusely enlarged thyroid without
focal abnormality (Fig 4). The
remainder of the neonatal hospital
course was relatively unremarkable
except for hyperbilirubinemia and
failing a hearing screen. Brainstem
auditory evoked response testing
demonstrated bilateral moderate
peripheral auditory abnormality for
the 500- to 4000-Hz frequency range,
likely sensorineural. The infant was
discharged from the hospital on
DOL 8. At 5 weeks old, he was alert
without constipation or difficulty
feeding. He was euthyroid (TSH
1.57 μIU/mL [normal 31 days to 12
months old: 0.62–8.05 μIU/mL] and
total T4 11.0 μg/dL [normal 1–12
months old: 7.2–15.6 μg/dL]).3 He
was fitted for bilateral hearing aids.
DISCUSSION
Fetal goiters are an uncommon
prenatal finding. In cases in which
thyroid-stimulating antibodies
are absent in the mother and
causes of dyshormonogenesis are
excluded, other etiologies for a fetal
goiter must be investigated. This
case illustrates the importance of
examining for iatrogenic causes for
fetal abnormalities. Our patient was
taking a natural thyroid supplement
that is equivalent to 62.5 times the
recommended daily allowance of
iodine in pregnancy. The excessive
iodine supplementation caused the
fetal goiter and hypothyroidism.
During pregnancy, iodine crosses
the placenta via active transport.5
Iodine is concentrated in the
thyroid gland and is essential for the
synthesis of thyroid hormones. The
recommended daily allowance for
pregnant women is 200 μg iodine
e3
subclinical hearing impairment in
approximately 25% of patients,
despite early and adequate
replacement treatment.12 The
critical period for development
of the cochlea starts at the end of
the first trimester of pregnancy
and continues to the first year of
postnatal life.13 Thyroid hormone
has been shown to regulate cochlear
development.14 Neonates diagnosed
with fetal goiter and suspected
in utero hypothyroidism warrant
careful follow-up over the first few
decades for hearing loss.
FIGURE 4
Postnatal ultrasound of the infant’s diffusely enlarged thyroid gland on DOL 6. The total mean volume
of the thyroid gland was 3.6 mL compared with the normal mean volume of 1.62 ± 0.41 mL for the
same age neonate.4
daily.6 Iodine toxicity can develop
when consuming >1.1 mg daily.7 In
healthy subjects, excessive intake
of iodine acutely inhibits thyroid
hormone secretion and temporarily
inhibits thyroid biosynthesis. After
prolonged exposure to excessive
iodine, organification and thyroid
hormone biosynthesis resume
in a normal fashion. This is also
known as escape from the WolffChaikoff effect.8,9 Unlike children
and adults, the immature fetal and
neonatal thyroid gland cannot
decrease intracellular iodine
transportation. The fetus therefore
remains hypothyroid. This effect
resolves when the excessive iodine
supplementation is removed.
It is important that clinicians
examine all patient medications,
including nutritional supplements.
As nutritional supplements are not
subject to standardized regulations
by the Food and Drug Administration,
patients may be unknowingly
consuming supratherapeutic doses
of potential fetal teratogens. A
e4
recent study by de Vasconcellos
et al10 described 8 children with
neonatal goiters secondary to a
compounded prenatal vitamin.
The vitamin contained 400 times
more than the recommended dose
of iodine in pregnancy. The goiters
were identified both prenatally
and confirmed by ultrasound after
delivery. In all cases, thyroid function
returned to normal after delivery or
when exposure to excessive iodine
was discontinued.
With regard to the bilateral hearing
loss, it is difficult to say whether this
is a consequence of the transient
fetal hypothyroidism. Deafness is
a known consequence of untreated
hypothyroidism. The risk of
hearing loss seems to be closely
associated with the severity of
hypothyroidism and is particularly
relevant in children with in
utero onset of hypothyroidism.11
In 1 cohort of patients with
congenital hypothyroid detected
by neonatal screening at 8 to 22
years of age, there was mild and
Fetal neck masses, such a goiter,
can compress the trachea,
leading to airway compromise at
delivery. As in this case, a fetal
MRI may serve as an adjunct to
ultrasound to better characterize
soft tissue masses, the impact of
masses on the trachea, and the
cartilaginous structures of the
upper airway.15 Furthermore, a
multidisciplinary team, including
pediatric anesthesiologist, pediatric
otolaryngologist, and neonatologist,
should be involved in delivery
planning. An EXIT procedure is
used to secure the neonatal airway
while fetal-placental circulation
is preserved in cases of airway
obstructions (eg, congenital airway
obstructions, laryngeal atresia,
micrognathia, fetal neck masses,
and intrathoracic masses).15 An
EXIT procedure is associated with
increased maternal hemorrhagic
morbidity and risk of cesarean
hysterectomy.15 However, it should
be considered and can decrease the
mortality of neonates when airway
compromise is possible.
Excessive maternal iodine
supplementation is a rare but
reversible cause of fetal goiter. This
case illustrates the importance
of examining patients’ use of
medications during pregnancy,
including naturopathic supplements,
as it may reveal the underlying cause
of a fetal anomaly and help determine
clinical management.
OVERCASH et al
ABBREVIATIONS
DOL: day of life
EXIT: ex utero intrapartum
treatment
T4: thyroxine
TSH: thyrotropin
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