Radioactive Iodine-Induced
Hyposalivation: Case Report
Qingcong Zeng, BS,* and Louis Mandel, DDSy
Radioactive iodine (131I) is used in the treatment of differentiated thyroid cancers. Collateral damage to the
salivary glands (SGs) can be anticipated. Standard therapeutic doses of 131I often cause SG obstructive
symptomatology and hyposalivation can develop with the higher 131I doses used for aggressive thyroid
malignancies with or without metastases.
Ó 2019 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 77:1837-1840, 2019
External beam radiation, for the treatment of oral ma-
lignancies, can be expected to cause collateral damage
to the salivary glands (SGs). Radiation sialadenitis with
hyposalivation is a well-known end result. Radioactive
iodine (131I) has a similar effect on the SGs. 131I plays a
key therapeutic role in the treatment of differentiated
papillary and follicular thyroid carcinomas. Differenti-
ated thyroid cancers represent 90% of all thyroid can-
cers.1 Approximately 57,000 cases were reported in
2017, with 75% of these cases involving female pa-
tients.2 Therapeutic 131I is orally administered and is
absorbed and concentrated by benign and malignant
thyroid cells. The radioactivity destroys these cells
because iodine is an inherent part of these cells’
normal metabolic activity. A major portion of the
administered 131I is secreted into the saliva by the
SGs. The concentration of iodide in the saliva has
been variously estimated to be 20 to 100 times that
found in the plasma.3-6
The SG transport molecule for 131I, the sodium
iodide symporter, resides in the basolateral membrane
of the SG’s striated ducts.2,7 In consequence, the
salivary ducts sustain more radiation damage than
the SG’s secreting parenchymal cells. The measured
131
I dose to the ductal epithelium has been reported
to be 3 to 4 times higher than the mean dose to the
SG parenchyma.8 Dosages no larger than 30 mCi,
generally used for Graves disease or multinodular
goiter, ordinarily do not cause SG symptomatology.
Received from Salivary Gland Center, Columbia University College of
Dental Medicine, New York, NY.
*Research Assistant, Salivary Gland Center; Third-Year Student,
Columbia University College of Dental Medicine.
yDirector, Salivary Gland Center; Associate Dean; Clinical
Professor, Oral and Maxillofacial Surgery, Columbia University
College of Dental Medicine.
Conflict of Interest Disclosures: Neither author has a relevant
financial relationship(s) with a commercial interest.
1837
The frequently administered therapeutic 131I dose of
75 to 100 mCi administered for differentiated thyroid
cancer can lead to short-term and long-term SG radia-
tion damage. Almost immediately after this 131I ther-
apy, 39% of patients develop SG swelling or pain.9
131
I radiation to the SG causes endothelial damage to
the glandular vasculature and an increase in vessel
wall permeability that initiates an intraglandular in-
flammatory infiltrate.10 Fortunately, within a few
days, resolution of this post-therapeutic inflammatory
process usually occurs and symptoms subside.3 How-
ever, with the passage of time, the damaging effect of
the ionizing radiation that has been incorporated into
the genetic structure of the cells becomes more
apparent in succeeding cell generations. Then, pro-
gressive damage to the more susceptible ductal
epithelium leads to narrowing of the luminal
passageway. As many as 67% of patients will
develop obstructive symptoms.6,11,12 Inflammatory
obstruction to salivary flow is manifested by
glandular swelling and pain, most evident during
periods of increased salivary demand, such as during
eating. In most patients, symptom resolution
eventually occurs, with only 5% of patients reporting
SG problems when seen 7 years after 131I
treatment.9 Although some ductal stricture from
inflammation inevitably develops, the resulting nar-
rowed lumen is apparently sufficient to accommodate
normal salivary demand.
Address correspondence and reprint requests to Dr Mandel:
Columbia University College of Dental Medicine, 630 West 168th
Street, New York, NY 10032; e-mail: lm7@columbia.edu
Received February 22 2019
Accepted March 22 2019
Ó 2019 American Association of Oral and Maxillofacial Surgeons
0278-2391/19/30358-1
https://doi.org/10.1016/j.joms.2019.03.032
1838 RADIOACTIVE IODINE-INDUCED HYPOSALIVATION

Aggressive thyroid malignancies, with or without
metastases, require higher doses of 131I. The secreting
parenchyma will be affected, and hyposalivation, with
its accompanying issues of mucositis, dysgeusia, oral
dryness, oral burning and dysphagia, becomes a pa-
tient complaint. Increased 131I dosages, mandated in
the presence of aggressive lesions, present a serious
SG issue. With the administration of 131I of at least
500 mCi, gross gland parenchymal destruction can
be anticipated.13,14 In consequence, patient
complaints focus on the presence of oral dryness
and the symptomatology associated with this
hyposalivation. Obstructive symptomatology will no
longer be evident because parenchymal salivary
production has been eliminated.
SG injury from 131I usually occurs in any combina-
tion that involves the parotid glands (PGs) or subman-
dibular SGs (SMSGs) unilaterally or bilaterally. The PG
is more frequently involved, with objective and subjec-
tive symptoms, than the SMSG.7,12,15 The serous cells
of the PG are more sensitive to 131I than the mucous
cells of the SMSG.6 Furthermore, the continuous
SMSG secretory salivary flow, even at rest, can serve
to clear the 131I more rapidly than what occurs in
the PG system.6 In addition, the SMSG’s mucus-
containing secretion can act as a protective mecha-
nism against cellular radiation damage.5,11 Minor SGs
that contain mucous acini will react to the 131I in the
same way as the SMSGs.
swallowing, and oral burning, she decided to seek
further care from her dentist.
Extraoral examination showed no swelling of any
SG. Palpation of the PGs and SMSGs caused no pain.
No cervical lymphadenopathy was present. Intraor-
ally, the mucosa appeared dry. After stimulation with
sour candy, the 2 PGs and 2 SMGs were aggressively
massaged extraorally while their orifices were
observed intraorally. No saliva was seen to exit from
any duct orifice. Furthermore, no visible Stensen
papillae were evident, reflecting a functional atrophy
that probably resulted from the longstanding persis-
tent hyposalivation (Fig 1). An increased incidence
of dental caries also was evident.
A scintigraphic examination, using the radioisotope
technetium-99m pertechnetate (TPT), was performed
to ascertain the status of the SGs. The time-and-activity
graph displayed total loss of activity of the right and
left PGs (Fig 2A) and right and left SMSGs (Fig 2B).
Discussion
The SGC evaluates patients who have 131I-induced
SG dysfunction using scintigraphic procedures. The
advantage of scintigraphy is that it allows the clinician
to visualize real-time activity of 4 glands (2 PGs and 2
SMSGs) simultaneously. The technique involves the
intravenous introduction of TPT, a radioisotope of mo-
lybdenum that emits nondestructive gamma radiation

Report of Case
A 78-year-old woman was referred to the Columbia
University College of Dental Medicine Salivary Gland
Center (SGC; New York, NY) by her dentist because
of a subjective complaint of dry mouth. Her medical
history indicated that she had been treated for a thy-
roid follicular carcinoma. Surgical removal of the ma-
lignancy and associated normal thyroid tissue was
performed in February 1996. In April 1996, 131I
75 mCi was administered. A routine examination in
December 1999 showed the presence of a lung metas-
tasis and an additional 131I dose of 298 mCi was given.
Because the metastasis did not regress, another 131I
dose (299 mCi) was given in May 2002. Currently,
because there is continued progression of the malig-
nancy, the patient is receiving the chemotherapeutic
agent lenvatinib. Her only other medication is the thy-
roid replacement hormone levothyroxine.
The patient had a history of intermittent swelling
and pain of the right and left PGs and SMSGs, but these
symptoms abated years previously. The patient stated
that a persistent 24-hour oral dryness had been FIGURE 1. Right buccal mucosa. Note absence of Stensen papilla.
present for approximately 10 years. Because she had Zeng and Mandel. Radioactive Iodine-Induced Hyposalivation. J
a dry mouth and a loss of taste, difficulty with Oral Maxillofac Surg 2019.
ZENG AND MANDEL 1839

FIGURE 2. A, Scintigraph shows failure of normal technetium-99m pertechnetate uptake by the right (R) and left (L) parotid glands and no
secretory elimination at the 10-minute mark. B, Scintigraph shows failure of normal technetium-99m pertechnetate uptake by the right (R)
and left (L) submandibular glands with no secretory elimination at the 10-minute mark.
Zeng and Mandel. Radioactive Iodine-Induced Hyposalivation. J Oral Maxillofac Surg 2019.

and has a 6-hour half-life. The TPT hones in on the SGs
such that its presence in the SGs can be imaged digi-
tally by a gamma camera. Then, a time-and-activity
graph can be plotted for 10 minutes. After 10 minutes,
the patient is instructed to suck on a sour candy to
stimulate secretory activity, which also is imaged and
plotted for 10 minutes.
Normal SGs will scintigraphically exhibit a steady
accumulation of TPT during the initial 10-minute
period (Fig 3). After 10 minutes, the secretory stimula-
tion from the sour candy is graphed and will show a
rapid SG evacuation of TPT. Because the present pa-
tient received a total 131I dose of 672 mCi, severe glan-
dular damage resulted. No functional activity in the
PGs or SMSGs was observed and this was imaged by
the flat-lining seen on scintigrams. There was a failure
of TPT uptake by the SGs followed by a complete
secretory failure.

FIGURE 3. Normal scintigraph displays normal technetium-99m pertechnetate uptake by the right (R) and left (L) parotid glands and normal
technetium-99m pertechnetate elimination at the 10-minute mark.
Zeng and Mandel. Radioactive Iodine-Induced Hyposalivation. J Oral Maxillofac Surg 2019.
1840
Unfortunately, the present patient had an aggressive
form of follicular thyroid cancer. Metastasis developed
and mandated increased dosages of 131I. Severe SG
damage resulted with loss of saliva and its functional
activity. Saliva acts to buffer the acids that lead to caries
and serves to remineralize teeth. Saliva also functions
to moisten food and facilitate its swallowing. With
the loss of saliva’s lubricant function, oral burning
develops. Dysgeusia develops because the serous
glands, adjacent to the taste buds, are damaged and
their secretions will fail to transmit food’s chemical
tastants to the taste buds.3 Direct radiation damage
to the taste buds also can play a role in the loss of taste.
Treatment
No treatment, other than palliative, can be offered
when there is total destruction of the functional activ-
ity of the SGs. Cholinergic stimulants, such as pilocar-
pine or cevimeline, are of no value because the
secreting parenchyma has been destroyed. Commer-
cial products are available to moisten and lubricate
the mucosa and mitigate the oral dryness and burning.
Fluoride therapy in the form of topical applications,
toothpaste, and mouthwash should be prescribed for
caries prevention.
Aggressive thyroid cancers require high dosages of
radioactive iodine. Because substantial amounts of
the ingested 131I are evacuated through the SGs, radia-
tion sialadenitis becomes an issue. The intensity of the
damage to the SGs is in direct proportion to the 131I
dosage. Dosages of at least 500 mCi lead to severe
loss of SG secretory activity and salivary functions.
RADIOACTIVE IODINE-INDUCED HYPOSALIVATION
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