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Iodine Research

Resource Network of The Iodine Movement

                         Iodine and the Body

Exocrine System

Glands of the body are classified as either endocrine or exocrine types.

Endocrine glands are the hormone producing structures of the body, such as the thyroid, adrenal, and pituitary
glands.  They secrete their products into the bloodstream.

Exocrine glands have ducts that connect to epithelial or surface cells.  For example, salivary glands open to the oral
cavity, sweat glands deposit their products onto the body surface, mammary gland secrete milk from the breast,
lacrimal glands secrete tears onto the surface of the eye, and glands in the gastrointestinal system secrete digestive
enzymes and other products into the gastrointestinal tube.

Many exocrine glands concentrate iodine and express the Sodium-Iodide Symporter (NIS).

Spitzweg et al investigate the expression of the Sodium-Iodide Symporter in several human exocrine glands,
including the salivary gland, lacrimal gland, gastric mucosa, choroid plexus, and lactating mammary gland.

Bakheet looks at iodine in tears secreted by the lacrimal gland in the eye.

Solans, Zettinig, and Nakada examines damage to the salivary and lacrimal glands caused by radioiodine

See also:
 Mouth, Breast, Skin, Eyes, Gastrointestinal System

Radioiodine secretion in tears.
Bakheet SM, Hammami MM, Hemidan A, Powe JE, Bajaafar F.
J Nucl Med. 1998 Aug;39(8):1452-4.

Lacrimal secretion of radioiodine has been suspected from previous scintigraphic observations. We
semiquantitated radioiodine secretion in the tears of a thyroid-ablated patient with an artificial eye
while the patient was on thyroxine treatment.

METHODS: After an oral dose of 555 MBq (15 mCi) 123I, 12 tear samples were collected
over 24 hr by using Schirmer papers. Radioactivity in each sample was determined in a
well counter 27 hr after radioiodine ingestion and was corrected for decay and counting

RESULTS: Radioactivity was detectable at 15 min and at up to 24 hr after radioiodine
ingestion and peaked at around 60 min (215 Bq/microl or 39 x 10(6)% of the administered
dose/microl. Considering a tear-flow rate of 1 microl/min, the total radioactivity secreted in
the first 4 hr was estimated to be 56 kBq, representing about 0.01% of the administered

CONCLUSION: An appreciable amount of ingested radioiodine could be secreted in tears.
The potential damage of the lacrimal gland after high doses of 131I treatment deserves
further study.

Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?
Nakada K, Ishibashi T, Takei T, Hirata K, Shinohara K, Katoh S, Zhao S, Tamaki N, Noguchi Y,
Noguchi S.
J Nucl Med. 2005 Feb;46(2):261-6.

Salivary gland dysfunction is one of the common side effects of high-dose radioiodine therapy for
thyroid cancer. The purpose of this study was to determine whether an early start of sucking lemon
candy decreases salivary gland injury after radioiodine therapy.

METHODS: The incidence of the side effects of radioiodine therapy on the salivary glands was
prospectively and longitudinally investigated in 2 groups of patients with postsurgical differentiated
thyroid cancer with varying regimens for sucking lemon candy. From August 1999 to October 2000,
116 consecutive patients were asked to suck 1 or 2 lemon candies every 2-3 h in the daytime of the
first 5 d after radioiodine therapy (group A). Lemon candy sucking was started within 1 h after
radioiodine ingestion. From November 2000 to June 2002, 139 consecutive patients (group B) were
asked to suck lemon candies in a manner similar to that of group A. In the group B, lemon candies
were withheld until 24 h after the ingestion of radioiodine. Patients with salivary gland disorders,
diabetes, collagen tissue diseases, or a previous history of radioiodine therapy or external irradiation
to the neck were excluded. Thus, 105 patients in group A and 125 patients in group B were available
for analysis. There were no statistical differences in the mean age (55.2 y vs. 58.5 y), average levels
of serum free thyroxine (l-3,5,3',5'-tetraiodothyronine) (0.40 ng/dL vs. 0.47 ng/dL), and the mean
dose of (131)I administered (3.96 GBq vs. 3.87 GBq) between the 2 groups. The onset of salivary
side effects was monitored during hospital admission and regular follow-up on the basis of interviews
with patients, a visual analog scale, and salivary gland scintigraphy using (99m)Tc-pertechnetate.
When a patient showed a persistent (>4 mo) dry mouth associated with a nonfunctioning pattern on
salivary gland scintigraphy, a diagnosis of xerostomia was established.

RESULTS: The incidences of sialoadenitis, hypogeusia or taste loss, and dry mouth with or without
repeated sialadenitis in group A versus group B were 63.8% versus 36.8% (P < 0.001), 39.0%
versus 25.6% (P < 0.01), and 23.8% versus 11.2% (P < 0.005), respectively. Permanent xerostomia
occurred in 15 patients in group A (14.3%) and 7 patients in group B (5.6%) (P < 0.05). In both
groups, bilateral involvement of the parotid gland was the most frequently seen and was followed by
bilateral involvement of the submandibular gland.

CONCLUSION: An early start of sucking lemon candy may induce a significant increase in salivary
gland damage. Lemon candy should not be given until 24 h after radioiodine therapy.

Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy.
Solans R, Bosch JA, Galofre P, Porta F, Rosello J, Selva-O'Callagan A, Vilardell M.
J Nucl Med. 2001 May;42(5):738-43.

Salivary gland dysfunction has been described in patients undergoing radioiodine therapy but
associated lacrimal gland dysfunction (sicca syndrome) has never been reported. We conducted a
prospective cohort study with follow-up for up to 3 y in a tertiary care university center to determine
the prevalence of sicca syndrome in patients after high-dose radioiodine treatment.

METHODS: From January 1990 to December 1995, all patients undergoing radioiodine therapy (n =
79) with a standard dose of 925 MBq to 18.5 GBq (25-500 mCi) were interviewed using a
standardized questionnaire to determine subjective ocular and oral dryness and were examined for
objective lacrimal and salivary gland dysfunction.

RESULTS: After radioiodine treatment, 32.9% of the patients reported subjective xerostomia and
25.3% reported subjective xerophthalmia in the first year of follow-up. Xerostomia persisted to the
second year of follow-up in 20.3% of cases and was still present >3 y after the last dose of
radioiodine in 15.2% of cases. Xerophthalmia persisted to the second year of follow-up in 17.7% of
cases and was still present in the third year of follow-up in 13.9% of cases. Severe xerostomia
occurred in 4 patients. Reduced salivary and lacrimal gland function was documented in 40 (50.6%)
and 14 (17.7%) of the 79 cases, respectively, in the first year of follow-up. Objective xerostomia
persisted in 13.9% of cases to the second year of follow-up and was still present in all patients >3 y
after the last radioiodine application. Keratoconjunctivitis sicca persisted in 11 patients (13.9%) to
the second year of follow-up but was only present in 6 patients (7.6%) >3 y after the last radioiodine
application. Additionally, 28/79 patients (35.4%) who had a normal salivary gland scintigraphy
previously showed reduced salivary gland function in the third year of follow-up. No significant
dependence on cumulative treatment was found for objective xerostomia or xerophthalmia, but doses
>11.1 GBq (300 mCi) were related to stage 3 dysfunction on salivary gland scintigraphy.

CONCLUSION: Salivary and lacrimal gland dysfunction (sicca syndrome) is relatively frequent after
radioiodine therapy. In most cases this is a transient side effect, but in some patients it may persist
for a long period or appear late.

Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands.
Spitzweg C, Joba W, Schriever K, Goellner JR, Morris JC, Heufelder AE.
J Clin Endocrinol Metab. 1999 Nov;84(11):4178-84.

The human sodium iodide symporter (hNIS) is an intrinsic transmembrane protein that mediates the
active transport of iodide across the basolateral membrane of thyroid follicular cells. In addition to
normally functioning thyroid tissue, various extrathyroidal tissues, including salivary gland, lacrimal
gland, gastric mucosa, choroid plexus, and lactating mammary gland, have been demonstrated to
accumulate iodide. After cloning and molecular characterization of the sodium iodide symporter,
expression of hNIS messenger ribonucleic acid has been detected in a broad range of extrathyroidal
tissues using Northern blot analysis and RT-PCR. In this study we used both monoclonal and
polyclonal antibodies directed against different portions of hNIS protein together with a highly
sensitive immunostaining technique to assess hNIS protein expression in tissue sections derived from
normal human salivary and lacrimal glands, pancreas, as well as gastric and colonic mucosa.
Immunohistochemical analysis of normal human salivary and lacrimal glands revealed marked hNIS
immunoreactivity in ductal cells and less intense staining of acinar cells. Further, immunostaining of
gastric and colonic mucosa showed marked hNIS immunoreactivity confined to chief and parietal cells
in gastric mucosa and to epithelial cells lining mucosal crypts in colonic mucosa. In normal human
pancreas, hNIS immunoreactivity was located in ductal cells, exocrine parenchymal cells, and
Langerhans islet cells. In conclusion, our study demonstrates the expression of hNIS protein by
several human exocrine glands, suggesting that iodide transport in these glands is a specific
property conferred by the expression of hNIS protein, which may serve important functions by
concentrating iodine in glandular secretions.

Long-term impairment of the lacrimal glands after radioiodine therapy: a cross-sectional study.
Zettinig G, Hanselmayer G, Fueger BJ, Hofmann A, Pirich C, Nepp J, Dudczak R.
Eur J Nucl Med Mol Imaging. 2002 Nov;29(11):1428-32. Epub 2002 Aug 28.
[abstract only]

Impairment of the lacrimal glands after external radiation has been well documented, but there are
only a few reports on the effects of radioiodine therapy on the lacrimal glands. Long-term effects of
high-dose radioiodine therapy on tear secretion have not previously been studied. We investigated
175 eyes of 88 patients with a history of radioiodine therapy for thyroid carcinoma (68 females, 20
males; mean age 55+/-16 years, range 17-81 years) and compared them with a sex- and
age-matched control group ( n=39). All patients had been given at least 2.96 GBq iodine-131
(maximal administered activity 22.3 GBq (131)I). An ophthalmological investigation was performed
64+/-71 months (range 3-317 months) after initial radioiodine therapy by a single ophthalmologist.
Lacrimal gland function was evaluated with three different function tests. External eye morphology
was considered, and detailed ophthalmological history-taking was performed. Patients with factors
known to affect lacrimal gland function (contact lenses, autoimmune disorders, history of additional
radiation exposure) were excluded from the study. A total of 81 patients (92%) had at least one
abnormal function test indicating impaired lacrimal gland function. Schirmer's tear test was
decreased (<10 mm/5 min) in 47 of the 88 patients and definitely abnormal (<5 mm/5 min) in 35
patients. A tear film break-up time of <10 s was found in 78 patients, and 62 patients had a definitely
abnormal break-up time of <5 s. The lacrimal lipid layer was impaired in 43 patients. The function
tests were all significantly altered in the study group as compared with the controls ( P<0.005,
P<0.001, P<0.001, respectively). Both subjective symptoms of dry eye ( P<0.01) and changes in the
external eye morphology ( P<0.001) were significantly more prevalent in the study group. Our
findings suggest that in the majority of patients, lacrimal gland function may be permanently impaired
after high-dose radioiodine therapy. All three layers of the tear film are involved and there is a
pronounced long-term effect on the tear film stability.