Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing LossRachael T. Overcash, MD, MPH, a, b Krishelle L. Marc-Aurele, MD, c Andrew D. Hull, MD, a Gladys A. Ramos, MDa

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 Maternal-

Fetal 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 fi nal

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 fi nal 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.

overcash@gmail.com

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 fi nancial relationships

relevant to this article to disclose.

FUNDING: No external funding.

POTENTIAL CONFLICT OF INTEREST: The authors

have indicated they have no potential confl icts of

interest to disclose.

Fetal goiter is a rare condition. It is

commonly due to maternal thyroid-

stimulating 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

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 × 3.3-

cm 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 “star-

gazing, ” 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

abstractA 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 × 3.3-

cm 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.

CASE REPORTPEDIATRICS Volume 137 , number 4 , April 2016 :e 20153722

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

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OVERCASH et al

identified. The differential diagnosis

for these ultrasound findings

included a teratoma, lymphangioma,

goiter, branchial cleft cyst, and

vascular malformation such as

hemangioma.

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.

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)

e2

FIGURE 1Axial 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.

FIGURE 2Sagittal view of fetal goiter (black arrow) on MRI (fi esta steady state free precession) at 29 weeks’ gestation.

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PEDIATRICS Volume 137 , number 4 , April 2016

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

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

FIGURE 3Axial 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.

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OVERCASH et al

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 Wolff-

Chaikoff 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

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

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.

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.

e4

FIGURE 4Postnatal 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

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PEDIATRICS Volume 137 , number 4 , April 2016

ABBREVIATIONS

DOL:  day of life

EXIT:  ex utero intrapartum

treatment

T4:  thyroxine

TSH:  thyrotropin

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DOI: 10.1542/peds.2015-3722 originally published online March 22, 2016; 2016;137;Pediatrics 

RamosRachael T. Overcash, Krishelle L. Marc-Aurele, Andrew D. Hull and Gladys A.

Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss

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Maternal Iodine Exposure: A Case of Fetal Goiter and Neonatal Hearing Loss

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