Skip to main content
NCBI home page
Journal of Healthcare Engineering logoLink to Journal of Healthcare Engineering
. 2022 Apr 14;2022:7640405. doi: 10.1155/2022/7640405

Quantitative Scintigraphy Evaluated the Relationship between 131I Therapy and Salivary Glands Function in DTC Patients: A Retrospective Analysis

Xiaolan Lv 1,2, Liang Yin 1,3, Weiming Wu 1, Ning Li 1, Ruyi Zhang 1, Xue Li 1, Qiang Jia 1, Jian Tan 1, Peng Wang 1, Xiangqian Zheng 4, Xianghui He 5, Chao Huang 6, Dihua Li 7, Yan Wang 8, Zhaowei Meng 1,✉
PMCID: PMC9023193  PMID: 35463665

Abstract

Purpose

Quantitative scintigraphy to evaluate salivary gland function changes in patients with differentiated thyroid cancer (DTC) after iodine-131 (131I) treatment.

Methods

A total of 458 patients with DTC grouped by sex and age were included. Salivary gland scintigraphy was performed to evaluate salivary gland function before and after 131I treatment. The uptake fraction (UF), uptake index (UI), and excretion fraction (EF) of two pairs of parotid glands and submandibular glands were measured and compared. The Chi-square test was conducted according to function impairment count.

Results

Salivary gland function in different age groups and sexes were quite different, especially for women <55 years old, who had decreased UF, UI, and EF of all four glands without basal injury. The secretion or uptake function of some salivary glands with basic function impairment before 131I treatment was increased after iodine treatment. Only a small percentage of males showed reduced functional parameters after several treatments. The most significant difference in the count of impairment for the four salivary glands were the first and third examinations, which was more evident in women. The submandibular gland had the most significant reduction in uptake.

Conclusion

Changes in salivary gland function are more common in young females being treated for DTC. Impairment of salivary gland function is correlated with the number of treatments and the cumulative dose of 131I. Some salivary gland functions impaired before 131I treatment were enhanced in the early treatment.

1. Introduction

Differentiated thyroid cancer (DTC) is a common endocrine malignancy. According to statistics, 900,590 people were diagnosed with thyroid cancer in the United States. 52,070 people are expected to be diagnosed with thyroid cancer in 2019 [1]. Surgical treatment of thyroid cancer followed by removal of residual thyroid using iodine-131 (131I) is a common treatment approach, but 131I can induce salivary gland damage [2–4]. 131I is absorbed on the membranes of thyroid follicular cells and cancer cells through the reactive sodium iodide transporter (NIS) [5]. Salivary glands expressing NIS can also absorb 131I, and the accumulation of salivary gland 131I is about 30 to 40 times that of plasma levels [6]. The radiation dose of high-concentration 131I is sufficient to cause salivary gland damage and affect their function [7].

Salivary gland dysfunction is mainly reflected in decreased saliva secretion. Saliva is essential for the preservation of oral health. Saliva's functions include buffering, lubricating, mineralizing, and cleaning oral tissues [8]. Saliva also has antibacterial, antiviral, and antifungal properties [9]. Changes in the quantity or quality of saliva can affect the integrity of the oral tissues leading to the appearance of conditions like dental caries, periodontal diseases, and various other oral and pharyngeal disorders [10, 11]. In addition, salivary gland dysfunction is characterized by difficulty swallowing, dental disease, and loss of taste. DTC patients who had one or more 131I treatments may experience the above discomfort [12–14]. Their quality of life was affected. Therefore, determining and protecting salivary gland function in DTC patients should not be ignored. There are many examinations to assess salivary gland function, including salivary gland scintigraphy with 99mTc-pertechnetate [3, 4, 15], neck ultrasonography [16], salivary flow rate measurement of the whole or individual gland [17]. 99mTc-pertechnetate is commonly used in hospitals. Because it can quantify the uptake or secretory from individual salivary glands and calculate their function [18–20].

Through salivary gland scintigraphy, we found that some patients had impaired salivary gland function before 131I treatment. We defined it as an impairment of the basic function of the salivary glands. The Impairment of basic function could be associated with different factors, including Sjögren syndrome [21, 22], salivary gland obstructive disease [23], salivary gland infection [24], obesity and diabetes [25, 26], aging [27, 28] and so on. The changes in the salivary gland's function in these patients after 131I treatment are worth discussing.

This study aimed to analyze the changes in salivary gland uptake and excretion function following 131I treatment. And to study the relationships between the function change and different genders, age groups. The results provide clinical guidance for the protection of salivary function in DTC patients undergoing 131I treatment.

2. Materials and Methods

2.1. Patients

A retrospective analysis of the hospital files from the Department of Nuclear Medicine of Tianjin Medical University General Hospital was in this study. The salivary gland scintigraphy parameters and inpatient treatment database of DTC patients from the hospital were used. We reviewed information for DTC patients who received 131I therapy from November 2014 to December 2018. All enrolled patients had two or more pre-hospital scintigraphy of salivary glands. A total of 458 patients with DTC grouped by sex and age were included. Patients with the above information missing were excluded. Total thyroidectomy was performed for all patients by thyroid surgeons, and DTC was diagnosed by postoperative pathology. According to the ATA Guidelines, we selected N1b or M1 DTC patients [2]. All patients received 131I treatment 6 weeks postoperatively. Before treatment with 131I, patients were advised to have a low-iodine diet for 3 weeks. After the first radioiodine treatment, patients in the study received one or more radioiodine treatments. Salivary gland function parameters were recorded by 370 MBq (10 mCi) 99mTc-Pertechnetate salivary gland scintillation before 131I treatment. The interval between each treatment was ∼6 months. The protocol for evaluating salivary gland scintigraphy is shown in Figure 1. Patients with residual thyroid tissue were given 2.96 to 5.55 GBq (30–150 mCi) dosages for each treatment [2, 29].

Figure 1.

Figure 1

Open in a new tab

Case follow-up process. Salivary glandular scintillation imaging data were collected from DTC patients before the first, second, third, and fourth 131I treatments. The group was compared according to the number of patients in each treatment course.

2.2. Salivary Gland Imaging Protocol

According to our previous reports, pre-ablation salivary gland imaging was performed under thyroid-stimulating hormone (TSH) stimulation in the morning, 4 h before the first 131I intake [3, 4]. Patients were asked to fast before salivary gland imaging. Single-photon emission computed tomography was performed on a Discovery NM/CT 670 (General Electric Medical Systems, Chicago, IL, USA) while subjects laid on their back. A low-energy, parallel hole, high-resolution collimator was used with a peak value of 140 keV and a window width of 20%. Each patient received 370 MBq 99mTc-pertechnetate intravenously through the cubital vein. After injection, the dynamic images were continuously shot on a 256 × 256 matrix at minute/frame with zoom 1.5 for 15 minutes. The patients were given 0.2 g oral vitamin C at the 8th minute after injection; they were instructed to chew quickly and then keep the tablet under the tongue for about 1 minute. To accurately calculate the delivered radioactivity dose, we measured the radioactivity count in the syringe before and after the injection. Patients underwent a radionuclide scan as described above before every 131I treatment. Salivary gland imaging was also performed under TSH stimulation.

2.3. Image Analysis

First, circular regions of interest (ROIs) were manually drawn on the parotid and submandibular glands. Parotid glands showed a similar unified background area in the bilateral temporal-orbital region, while submandibular glands appeared as a similar unified background area in the bilateral supraclavicular region. The sizes and positions of these ROIs remained the same for each scanning session. An imaging system was used to generate time-activity curves for 99mTc-pertechnetate uptake and excretion in counts per minute. Based on these ROIs counts and the subsequent time-activity curves, the salivary gland functional indicators were derived using the following modified formulas [3, 4, 30, 31] (Figure 2):

Figure 2.

Figure 2

Open in a new tab

Physiological uptake and excretion of 99mTc-pertechnetate in parotid and submandibular salivary glands detected by dynamic salivary gland scintigraphy. (a) A clear depiction of the ROIs and ROIs of the salivary and mandibular glands was obtained from all frames. (b) The parotid gland was in the bilateral temporal-orbital region, and the mandibular gland was in the bilateral supraclavicular region to draw similar background areas, and the background ROIs count was recorded. (c-d) Time-activity curve of each salivary gland. The ordinate of a1-a4 corresponds to the maximum minute count of each salivary gland. The ordinate of b1- b4 corresponds to the count of each salivary gland at the minimum uptake minute after vitamin C.

2.3.1. Uptake Fraction (UF)

UF =  (salivary gland maximum count minute–salivary gland background count corresponding to maximum count minute)/(count in the syringe before injection–count in the syringe after injection)

2.3.2. Uptake Index (UI)

UI = (salivary gland maximum uptake count minute–salivary gland background count corresponding to maximum uptake count minute)/salivary gland background count corresponding to maximum uptake count minute

2.3.3. Excretion Fraction (EF)

EF  = (salivary gland maximum uptake count minute–salivary gland minimum uptake count minute after vitamin C)/salivary gland background count corresponding to maximum uptake count minute

UI and UF reflect the uptake function of salivary glands, while EF reflects the secretion function.

2.4. Diagnostic Criteria for Salivary Gland Function

Salivary gland function impairment was established based on the diagnostic criteria of the Department of Nuclear Medicine, Tianjin Medical University General Hospital, with reference to previous studies and modified in our institute [18, 19, 32, 33]. Parameters obtained by salivary scintigraphy, the peak uptake (maximum salivary gland uptake count/second count at peak uptake) was set to <50 counts/s with reduced intake function, and EF was set to <30% with reduced secretory function. A reduced diagnosis of either or both of these above salivary glands is dysfunction. The patients with salivary gland dysfunction before the first admission were those with impaired basic salivary gland function.

2.5. Statistical Analysis

All data for males and females were analyzed separately and are presented as either mean ± standard deviation or median (upper quartile, lower quartiles). Statistical analysis was performed by using Statistical Package for Social Sciences (SPSS version 25.0, IBM Corp., Armonk, NY, USA) software. Mann-Whitney U tests were used to compare values of the same patient before and after the first treatment. Kruskal-Wallis tests were performed to evaluate and compare salivary gland function in patients who underwent multiple 131I treatments. After dividing men and women into separate groups, the distribution of salivary gland injuries before the first treatment and before the second to fourth treatments were analyzed by chi-square test.

3. Results

Among the 458 patients, most (72.9%) were female with a mean age of 46 ± 12 years (range 14–76 years). The lowest and highest doses of 131I were 30 and 550 mCi, respectively. Patient demographic data are summarized in Table 1.

Table 1.

Clinical characteristics of total patients.

Characteristic Total Male Female P
Age (years) 46 ± 12/14–76 46 ± 12/22–75 45 ± 12/14–76 0.442
Number/percentage   124/27% 334/73%  
131I activity (mCi) 128 ± 78/30–550 131 ± 68/30–450 126 ± 80/30–550 0.145
Open in a new tab

Age and 131I activity are stated as median ± standard deviation/range.

From the scintigraphy examinations, the analysis according to age and sex groups evidenced salivary gland function is more sensitive in females than in males. The sensitivity of salivary gland function was ranked from large to small, in order of <55 years female, ≥55 years female, <55 years male, ≥55 years male (p = 0.05). After treatment with 131I, the UI, UF, or EF values of patients without impairment of basic salivary gland function tended to decrease. The secretion or uptake function of some salivary glands with basic function impairment before 131I treatment was increased after iodine treatment. Table S1 summarizes the number of patients, age distribution, and cumulative dose before one or more 131I treatments. The UI, UF, and EF of each group were compared before and after 131I treatment (Tables 2–4).

Table 2.

Comparison of salivary gland function in patients before secondary treatmen.

Scintigraphic parameters Male under 55 years Male older than or equal to 55 years Female under 55 years Female older than or equal to 55 years
Damage before treatment After firsttreatment P No damage before treatment After firsttreatment P Damage before treatment After firsttreatment P No damage before treatment After firsttreatment P Damage before treatment After firsttreatment P No damage before treatment After firsttreatment P Damage before treatment After firsttreatment P No damage before treatment After firsttreatment P
RP Number:6 Number:83 Number:2 Number:32 Number:13 Number:244 Number:4 Number:74
UF 0.039 (0.027–0.071) 0.057 (0.025–0.093) 0.173 0.043 (0.031–0.054) 0.039 (0.030–0.058) 0.806 0.016 (0.011–0.014) 0.018 (0.013–0.014) 0.180 0.047 (0.026–0.066) 0.043 (0.025–0.056) 0.100 0.023 (0.016–0.049) 0.043 (0.022–0.051) 0.116 0.043 (0.032–0.057) 0.038 (0.030–0.049) 0.000 0.025 (0.010–0.044) 0.027 (0.015–0.036) 0.715 0.047 (0.034–0.058) 0.037 (0.029–0.057) 0.218
UI 1.792 (1.337–2.293) 2.448 (1.117–4.080) 0.116 1.814 (1.425–2.377) 1.806 (1.424–2.423) 0.799 0.967 (0.589–0.862) 0.960 (0.707–0.732) 0.655 1.787 (1.176–2.175) 1.685 (0.974–1.949) 0.104 1.714 (1.221–2.363) 1.946 (1.364–2.643) 0.133 2.105 (1.621–2.618) 1.920 (1.467–2.369) 0.000 1.314 (0.774–2.224) 1.169 (0.836–1.466) 0.465 1.868 (1.514–2.604) 1.712 (1.349–2.410) 0.243
EF 0.109 (0.070–0.218) 0.501 (0.292–0.613) 0.046 0.473 (0.412–0.546) 0.461 (0.354–0.539) 0.064 0.306 (0.190–0.270) 0.268 (0.195–0.207) 0.655 0.444 (0.361–0.488) 0.396 (0.302–0.513) 0.161 0.316 (0.118–0.437) 0.465 (0.241–0.521) 0.055 0.496 (0.428–0.560) 0.467 (0.404–0.533) 0.001 0.176 (0.091–0.255) 0.359 (0.143–0.473) 0.144 0.508 (0.444–0.556) 0.475 (0.409–0.541) 0.113
LP Number:3 Number:86 Number:2 Number:32 Number:17 Number:240 Number:8 Number:70
UF 0.034 (0.019–0.048) 0.036 (0.016–0.040) 0.593 0.039 (0.030–0.050) 0.036 (0.027–0.050) 0.113 0.023 (0.011–0.023) 0.031 (0.012–0.034) 0.180 0.044 (0.034–0.072) 0.045 (0.025–0.067) 0.197 0.023 (0.013–0.036) 0.032 (0.020–0.048) 0.407 0.038 (0.029–0.053) 0.036 (0.028–0.048) 0.000 0.020 (0.011–0.042) 0.031 (0.023–0.047) 0.069 0.044 (0.030–0.061) 0.035 (0.024–0.047) 0.000
UI 0.805 (0.724–1.409) 1.197 (0.588–1.633) 0.285 1.874 (1.346–2.240) 1.689 (1.288–2.142) 0.079 1.072 (0.594–1.014) 1.312 (0.732–1.237) 0.180 1.858 (1.388–2.379) 1.567 (1.261–2.528) 0.443 1.465 (1.308–2.291) 1.770 (1.368–2.305) 0.227 2.013 (1.569–2.548) 1.841 (1.464–2.347) 0.000 1.464 (0.940–2.044) 1.560 (1.012–2.049) 0.401 2.050 (1.427–2.531) 1.630 (1.243–2.134) 0.005
EF 0.124 (0.104–0.154) 0.418 (0.132–0.443) 0.109 0.486 (0.427–0.544) 0.465 (0.377–0.549) 0.043 0.198 (0.053–0.244) 0.390 (0.227–0.358) 0.655 0.440 (0.359–0.511) 0.397 (0.304–0.498) 0.061 0.225 (0.120–0.357) 0.383 (0.339–0.467) 0.001 0.494 (0.420–0.564) 0.468 (0.394–0.535) 0.000 0.188 (0.167–0.240) 0.390 (0.261–0.487) 0.208 0.504 (0.432–0.588) 0.472 (0.366–0.535) 0.008
RS Number:9 Number:80 Number:3 Number:31 Number:39 Number:218 Number:5 Number:73
UF 0.033 (0.023–0.049) 0.024 (0.021–0.046) 0.767 0.058 (0.042–.0766) 0.048 (0.038–0.062) 0.000 0.023 (0.023–0.030) 0.036 (0.021–0.036) 0.285 0.057 (0.048–0.067) 0.045 (0.038–0.063) 0.011 0.034 (0.028–0.042) 0.032 (0.026–0.049) 0.944 0.047 (0.035–0.061) 0.042 (0.033–0.052) 0.000 0.010 (0.009–0.026) 0.019 (0.015–0.029) 0.345 0.062 (0.050–0.078) 0.055 (0.047–0.070) 0.006
UI 2.156 (1.363–2.733) 1.662 (1.297–2.530) 0.767 2.984 (2.540–3.957) 2.736 (2.209–3.705) 0.016 1.736 (0.886–1.989) 1.883 (1.282–2.093) 0.285 3.074 (2.399–3.531) 2.604 (2.127–3.239) 0.050 1.780 (1.358–2.158) 2.018 (1.582–2.324) 0.024 2.490 (2.002–3.307) 2.401 (1.997–2.945) 0.001 1.205 (.699–1.960) 1.402 (0.846–1.937) 0.893 3.034 (2.607–3.986) 2.923 (2.405–3.742) 0.008
EF 0.171 (0.157–0.190) 0.194 (0.175–0.254) 0.066 0.388 (0.313–0.470) 0.347 (0.256–0.444) 0.020 0.152 (0.038–0.281) 0.196 (0.050–0.358) 0.593 0.374 (0.304–0.421) 0.339 (0.238–0.400) 0.264 0.157 (0.116–0.181) 0.255 (0.180–0.341) 0.000 0.377 (0.285–0.457) 0.344 (0.264–0.413) 0.000 0.132 (0.072–0.150) 0.174 (0.090–0.257) 0.043 0.432 (0.338–0.520) 0.383 (0.290–0.488) 0.005
LS Number:10 Number:79 One case Number:31 Number:50 Number:207 Number:7 Number:71
UF 0.027 (0.020–0.034) 0.025 (0.021–0.041) 0.241 0.052 (0.044–0.071) 0.045 (0.035–0.059) 0.000       0.061 (0.045–0.069) 0.048 (0.040–0.066) 0.010 0.029 (0.024–0.035) 0.029 (0.023–0.037) 0.490 0.045 (0.035–0.060) 0.042 (0.032–0.053) 0.000 0.017 (0.012–0.033) 0.022 (0.018–0.034) 0.398 0.061 (0.044–0.082) 0.050 (0.036–0.062) 0.000
UI 1.882 (1.247–2.158) 1.794 (1.499–2.296) 0.139 3.056 (2.488–4.031) 2.914 (2.371–3.532) 0.055       3.1515 (2.683–3.707) 2.973 (2.481–3.797) 0.348 1.917 (1.347–2.616) 2.015 (1.626–2.548) 0.420 2.877 (2.125–3.569) 2.630 (2.045–3.304) 0.004 1.974 (1.368–2.713) 2.239 (1.420–2.505) 0.735 3.120 (2.372–4.358) 2.809 (2.365–3.828) 0.003
EF 0.168 (0.149–0.187) 0.192 (0.134–0.251) 0.110 0.377 (0.282–0.460) 0.343 (0.236–0.425) 0.005       0.362 (0.290–0.432) 0.345 (0.252–0.423) 0.367 0.173 (0.139–0.198) 0.212 (0.171–0.291) 0.002 0.380 (0.306–0.475) 0.353 (0.277–0.428) 0.000 0.114 (0.063–0.174) 0.192 (0.142–0.336) 0.128 0.440 (0.324–0.499) 0.383 (0.275–0.462) 0.000
Open in a new tab

UF, UI, EF stated as median (upper quartile, lower quartiles), RP: Right parotid; LP: Left parotid; RS: Right submandibular; LS: Left submandibular; UF: Uptake fraction; UI: Uptake index; EF: Excretion fraction.

Table 3.

Comparison of salivary gland function in patients before third treatment.

Scintigraphic parameters Male group before third treatment Female group before third treatment
Damage before treatment After first treatment After second treatment P No damage before treatment After first treatment After second treatment P Damage before treatment After first treatment After second treatment P No damage before treatment After first treatment After second treatment P
RP Number: 2 Number: 29 Number: 2 Number: 86
UF 0.034 (0.018–0.033) 0.057 (0.019–0.067) 0.044 (0.012–0.055) 0.223 0.050 (0.031–0.068) 0.049 (0.032–0.060) 0.043 (0.026–0.061) 0.485 0.037 (0.010–0.045) 0.033 (0.010–0.039) 0.028 (0.008–0.034) 0.135 0.042 (0.031–0.055) 0.037 (0.028–0.048) 0.032 (0.021–0.041) 0.000
III-II 0.005 III-I 0.000 ⋯ II-I 0.081
UI 1.844 (1.054–1.712) 2.967 (0.865–3.586) 2.387 (0.864–2.717) 0.607 1.867 (1.527–2.391) 1.898 (1.440–2.819) 2.016 (1.277–3.038) 0.485 1.356 (0.673–1.360) 1.247 (0.533–1.336) 1.464 (0.588–1.607) 0.223 1.952 (1.549–2.479) 1.789 (1.460–2.188) 1.581 (1.137–2.102) 0.000
III-II 0.014 III-I 0.000 II-I 0.098
EF 0.254 (0.064–0.317) 0.506 (0.304–0.455) 0.299 (0.148–0.300) 0.607 0.486 (0.433–0.544) 0.478 (0.352–0.581) 0.493 (0.340–0.579) 0.422 0.194 (0.055–0.237) 0.418 (0.221–0.406) 0.412 (0.222–0.395) 1.000 0.485 (0.415–0.552) 0.4715 (0.419–0.539) 0.420 (0.246–0.521) 0.002
III-II0.036 III-I 0.002 II-I 1.000
LP No case Number: 31 Number: 5 Number: 83
UF         0.041 (0.035–0.065) 0.045 (0.033–0.056) 0.036 (0.027–0.053) 0.206 0.019 (0.009–0.025) 0.025 (0.021–0.039) 0.021 (0.013–0.040) 0.165 0.040 (0.029–0.051) 0.034 (0.027–0.045) 0.032 (0.021–0.042) 0.000
III-II 0.309 III-I 0.000 II-I 0.016
UI         1.971 (1.523–2.460) 1.897 (1.348–2.457) 1.615 (1.359–2.576) 0.597 0.861 (0.687–1.776) 1.164 (1.010–1.879) 1.332 (.916–2.084) 0.247 2.006 (1.393–2.281) 1.717 (1.319–2.143) 1.686 (1.231–2.194) 0.008
III-II 1.000 III-I 0.020 II-I 0.025
EF         0.510 (0.442–0.558) 0.464 (0.402–0.550) 0.455 (0.347–0.545) 0.086 0.166 (0.102–0.382) 0.368 (0.292–0.439) 0.328 (0.173–0.458) 0.247 0.479 (0.420–0.544) 0.472 (0.394–0.523) 0.423 (0.326–0.514) 0.010
III-II 0.392 III-I 0.008 II-I 0.392
RS Number: 2 Number: 29 Number: 6 Number: 82
UF 0.034 (0.017–0.033) 0.033 (0.016–0.034) 0.032 (0.021–0.027) 1.000 0.058 (0.046–0.080) 0.054 (0.042–0.066) 0.051 (0.038–0.065) 0.018 0.050 (0.033–0.064) 0.044 (0.032–0.068) 0.044 (0.018–0.074) 0.607 0.052 (0.039–0.068) 0.048 (0.035–0.057) 0.043 (0.034–0.054) 0.000
III-II 1.000 III-I 0.017 II-I 0.147   III-II 0.823 III-I 0.000 II-I 0.004
UI 1.553 (0.664–1.665) 1.821 (0.961–1.770) 1.636 (1.189–1.265) 0.607 3.171 (2.438–3.936) 3.105 (2.284–3.663) 3.052 (2.415–3.624) 0.639 1.650 (1.266–2.771) 2.251 (2.099–3.090) 2.024 (1.318–3.273) 0.115 2.685 (2.161–3.528) 2.715 (2.021–3.318) 2.395 (2.010–3.092) 0.011
III-II 0.930 III-I 0.009 II-I 0.153
EF 0.096 (0.029–0.115) 0.122 (0.038–0.146) 0.073 (0.032–0.078) 0.223 0.381 (0.335–0.467) 0.375 (0.271–0.416) 0.396 (0.318–0.468) 0.343 0.159 (0.122–0.169) 0.339 (0.248–0.382) 0.343 (0.191–0.439) 0.042 0.404 (0.308–0.498) 0.367 (0.291–0.435) 0.332 (0.242–0.430) 0.000
III-II 0.773 III-I 0.021 II-I 0.043 b III-II 0.414 III-I0 .000 II-I0 .024
LS Number: 2 Number: 29 Number: 9 Number: 79
UF 0.031 (0.011–0.036) 0.033 (0.009–0.040) 0.023 (0.009–0.025) 0.607 0.056 (0.044–0.079) 0.048 (0.040–0.065) 0.050 (0.040–0.059) 0.024 0.033 (0.023–0.051) 0.034 (0.020–0.040) 0.030 (0.021–0.043) 0.895 0.050 (0.039–0.068) 0.045 (0.034–0.055) 0.041 (0.033–0.054) 0.000
III-II 1.000 III-I 0.018 II-I 0.018 III-II0.529 III-I 0.000 II-I 0.016
UI 1.482 (0.656–1.568) 1.570 (0.645–1.711) 1.030 (0.421–1.125) 0.223 3.584 (2.667–4.089) 3.236 (2.655–3.797) 3.053 (2.546–3.685) 0.166 1.891 (1.437–2.864) 2.019 (1.591–2.928) 1.932 (1.408–2.687) 0.641 2.979 (2.219–3.580) 2.687 (2.140–3.362) 2.542 (1.977–3.191) 0.003
III-II 1.000 III-I 0.003 II-I .051
EF 0.169 (0.123–0.131) 0.072 (0.000–0.108) 0.034 (0.016–0.034) 0.223 0.418 (0.316–0.492) 0.372 (0.295–0.436) 0.404 (0.321–0.528) 0.166 0.169 (0.119–0.199) 0.336 (0.229–0.386) 0.235 (0.165–0.386) 0.050 0.395 (0.300–0.499) 0.365 (0.273–0.444) 0.323 (0.233–0.435) 0.000
Open in a new tab

UF, UI, EF stated as median (upper quartile, lower quartiles). Examination before first, second and third treatments expressed as I, II, and III. The values were p values after pairwise comparison of I, II, III. RP: Right parotid; LP: Left parotid; RS: Right submandibular; LS: Left submandibular; UF: Uptake fraction; UI: Uptake index; EF: Excretion fraction.

Table 4.

Comparison of salivary gland function in patients before fourth treatment.

Scintigraphy parameters Male group before fourth treatment number: 6 Female group before fourth treatment number: 8
Before treatment After first treatment After second treatment After third treatment P Before treatment After first treatment After second treatment After third treatment P
RP                    
UF 0.054 (0.024–0.072) 0.072 (0.035–0.089) 0.051 (0.025–0.077) 0.052 (0.015–0.076) 0.896 0.047 (0.043–0.056) 0.032 (0.031–0.046) 0.033 (0.018–0.037) 0.010 (0.009–0.042) 0.013
VI-III 1.000 VI-II.231 VI-I .011 III-II 1.000 III-I .231 II-1 1.000
UI 2.237 (1.492–2.725） 2.3137 (1.691–3.522） 2.252 (1.425–3.257） 2.127 (1.323–2.668） 0.706 2.371 (1.860–2.885) 1.690 (1.537–2.151) 1.388 (0.808–1.844) 0.707 (0.529–1.887) 0.003
VI-III 1.000 VI-II0.317 VI-I .003 III-II 1.000 III-I 0.040 II-1 0.728
EF 0.485 (0.330–0.559） 0.542 (0.460–0.705） 0.458 (0.364–0.547） 0.403 (0.004–0.548） 0.204 0.543 (0.500–0.567） 0.478 (0.439–0.487） 0.158 (0.023–0.446） 0.050 (0.022–0.407） 0.001
VI-III 1.000 VI-II0.071 VI-I .006 III-II 0.199 III-I 0.022 II-1 1.000
LP                    
UF 0.040 (0.035–0.065） 0.052 (0.039–0.067) 0.041 (0.029–0.070) 0.031 (0.010–0.045) 0.849 0.041 (0.035–0.050） 0.035 (0.027–0.048) 0.033 (0.026–0.044) 0.025 (0.018–.035) 0.034
VI-III 0.137 VI-II 0.231 VI-I 0.043 III-II 1.000 III-I 1.000 II-1 1.000
UI 1.958 (1.661–2.357) 2.3628 (1.468–2.616) 1.623 (1.307–3.080) 1.675 (1.213–1.995) 0.978 2.051 (1.765–2.396) 1.684 (1.534–2.175) 1.635 (0.963–2.104) 1.576 (0.472–2.029) 0.010
VI-III 1.000 VI-II 1.000 VI-I .040 III-II 1.000 III-I 0.012 II-I0.317
EF 0.515 (0.480–0.589) 0.487 (0.385–0.575) 0.419 (0.216–0.548) 0.287 (0.047–0.48) 0.038 0.475 (0.454–0.526) 0.445 (0.297–0.485) 0.411 (0.031–0.501) 0.429 (0.016–0.518) 0.522
I-III 1.000 VI-II 1.000 VI-I 0.044 III-II 1.000 III-1 0.152 II-1 1.000
RS                    
UF 0.053 (0.040–0.064) 0.057 (0.036–0.076) 0.050 (0.030–0.067) 0.040 (0.014–0.076) 0.284 0.052 (0.041–0.059) 0.039 (0.035–0.048) 0.043 (0.035–0.054) 0.037 (0.030–0.044) 0.021
VI-III .043 VI-II .586 VI-I .043 III-II 1.000 III-I 1.000 II-1 1.000
UI 2.147 (1.884–2.778) 3.041 (2.015–3.985) 2.703 (1.927–3.185) 2.726 (1.660–4.742) 0.572 2.988 (2.479–3.495) 2.465 (2.125–3.067) 2.649 (2.306–2.857) 2.447 (2.239–2.601) 0.119
EF 0.386 (0.338–0.444) 0.352 (0.246–0.471) 0.394 (0.315–0.466) 0.422 (0.181–0.475) 0.940 0.437 (0.373–0.455) 0.282 (0.254–0.352) 0.284 (0.218–0.405) 0.348 (0.143–0.437) 0.010
VI-III 1.000 VI-II 1.000 VI-I 0.317 III-II 1.000 III-I0.040 II-1 0.012
LS                    
UF 0.052 (0.044–0.056) 0.045 (0.043–0.078) 0.054 (0.041–0.063) 0.045 (0.015–0.070) 0.849 0.049 (0.042–0.056) 0.042 (0.030–0.047) 0.042 (0.034–0.049) 0.037 (0.030–0.040) 0.392
UI 2.605 (1.676–3.068) 3.420 (2.807–3.783) 3.023 (2.450–3.487) 2.904 (2.145–3.613) 0.706 2.550 (2.338–3.107) 2.620 (1.897–3.204) 2.666 (2.135–3.045) 2.472 (2.344–2.949) 0.789
EF 0.397 (0.350–0.456) 0.371 (0.255–0.427) 0.420 (0.297–0.504) 0.376 (0.166–0.453) 0.392 0.332 (0.269–0.407) 0.289 (0.259–0.355) 0.274 (0.194–0.405) 0.327 (0.129–0.415) 0.327
Open in a new tab

UF, UI, EF stated as median (upper quartile, lower quartiles). Examination before first, second, and third treatments expressed as I, II, III, and IV. The values were P values after pairwise comparison of I, II, III, IV. RP: Right parotid; LP: Left parotid; RS: Right submandibular; LS: Left submandibular; UF: Uptake fraction; UI: Uptake index; EF: Excretion fraction.

We found that the difference between the first and third injury counts of salivary gland damage on salivary gland scintigraphy tests before hospitalization was the most significant. There were statistically significant differences between the four salivary glands in both the male and female groups. It was more pronounced in the female group (female, P=0.001; male, P < 0.05). The percentage of damaged salivary glands increased with the number of treatments in both sexes, while the percentage of normal salivary glands gradually decreased (Table 5, Figure 1S). The cumulative dose of 131I received by patients over several treatments is shown in Figure 2S. Chi-square test was performed to determine the relationship between the number of patients by sex and the impairment of salivary gland function before each 131I treatment (Table S2). There was a statistical difference in the left submandibular gland injury count between sexes before the first treatment (p < 0.05).

Table 5.

The number of salivary gland injuries before the last three treatments compared with the first treatment.

Scintigraphic parameters Male Female
Damage First Second P First Third P First Fourth P First Second P First Third P First Fourth P
RP Hurt 8 (6.5%) 8 (6.5%) 1.000 8 (6.5%) 8 (25.8%) 0.005 8 (6.5%) 2 (33.3%) 0.069 17 (5.1%) 16 (5.1%) 0.859 17 (5.1%) 29 (33%) 0.001 17 (5.1%) 5 (62.5%) 0.001
No hurt 115 (93.5%) 115 (93.5%) 115 (93.5%) 23 (74.2%) 115 (93.5%) 4 (66.7%) 318 (94.9%) 319 (94.9%) 318 (94.9%) 59 (67%) 318 (94.9%) 3 (37.5%)
LP Hurt 5 (4.1%) 9 (7.3%) 0.271 5 (4.1%) 7 (22.6%) 0.003 5 (4.1%) 3 (50%) 0.003 25 (7.5%) 23 (6.9%) 0.881 25 (7.5%) 24 (27.3%) 0.001 25 (7.5%) 2 (25%) 0.125
No hurt 118 (95.9%) 114 (92.7%) 118 (95.9%) 24 (87.4%) 118 (95.9%) 3 (50%) 310 (92.5%) 312 (93.1%) 310 (92.5%) 64 (72.7%) 310 (92.5%) 6 (75%)
RS Hurt 12 (9.8%) 19 (15.4%) 0.179 12 (9.%) 8 (25.8%) 0.032 12 (9.8%) 2 (33.3%) 0.128 44 (13.1%) 48 (14.3%) 0.653 44 (13.1%) 36 (40.9%) 0.001 44 (13.1%) 2 (25%) 0.292
No hurt 111 (90.2%) 104 (84.6%) 111 (90.2%) 23 (74.2%) 111 (90.2%) 4 (66.7%) 291 (86.9%) 287 (85.7%) 291 (86.9%) 52 (59.1%) 291 (86.9%) 6 (75%)
LS Hurt 11 (8.9%) 22 (17.9%) 0.040 11 (8.9%) 8 (25.8%) 0.027 11 (8.9%) 2 (33.3%) 0.112 57 (17%) 62 (18.5%) 0.613 57 (17%) 39 (44.3%) 0.001 57 (17%) 4 (50%) 0.036
No hurt 112 (91.1%) 101 (82.1%) 112 (91.1%) 23 (74.2%) 112 (91.1%) 4 (66.7%) 278 (83%) 273 (81.5%) 278 (83%) 49 (55.7%) 278 (83%) 4 (50%)
Open in a new tab

The sequence number of examinations before treatments. Expressed as number of cases (values of number of cases/total cases of this examination before treatments ×  100%). RP: Right parotid; LP: Left parotid; RS: Right submandibular; LS: Left submandibular.

4. Discussion

Salivary gland damage is a common manifestation of DTC patients after 131I therapy [34]. 131I is mainly concentrated in the duct system of the salivary glands. The radiation causes debris buildup that narrows the lumen, and this obstruction can lead to an injurious process that results in glandular degeneration. Salivary gland scintigraphy examination is necessary for the objective evaluation of the reproducibility of salivary gland function [20]. These measurement parameters mainly assess gland uptake and secretion capacity [15, 35, 36]. We performed salivary gland scintigraphy to identify relevant salivary gland parameters and then analyzed the factors that affect salivary gland function changes in DTC patients after each 131I treatment.

4.1. Sex and Age

By comparing salivary glands without basic functional impairment, we found that functional changes were related to age and sex. The salivary glands of younger patients were more sensitive to 131I treatment than older patients, and female patients were more likely to show decreased function. Other studies have examined age- and sex-dependent differences in salivary gland function changes. Liu et al. assessed iodine dynamics and salivary gland dosimetry after 131I treatment and showed that women's parotid iodine intake was often higher than men's [37]. This suggests that female salivary glands are more susceptible to radiation, leading to decreased function following 131I treatment. Almeida et al. found that patient sex was associated with the uptake phase on salivary glands scintigraphy. Intake of all major salivary gland was decreased in men compared with women. Patient age was the strongest predictor of parotid gland dysfunction as it affects the stage of parotid gland uptake and elimination on salivary gland scintigraphy [38]. Another study revealed the presence of epidermal and nerve growth factors (EGF and NGF) in salivary glands and described their roles in cell growth and differentiation. They are detected at higher levels in the submandibular glands of males than females [39], indicating that male salivary gland cells have stronger repair and regeneration abilities. Animal studies showed sex-attributed differences in wound healing patterns in submandibular glands between male and female mice. In males, the number of convoluted tubules rich in EGF and NGF (involved in cell proliferation and neurogenesis, respectively) was higher than that in females [40, 41]. These sex- differences observed in mice may help explain why the incidence of salivary gland disease tends to be much higher in women than in men (i.e., approximately 9:1) [42].

4.2. Different Basic Functions

Before the first 131I treatment, we selected patients with basic impairment of salivary gland function. After the first 131I treatment, some salivary gland parameters were different in the female group, with most changes in the group younger than 55 years old. After the second 131I treatment, the bilateral submandibular gland EF values were different in females but not males. Interestingly, these altered functional parameters all showed an upward trend rather than the expected decline. We consider that this may be related to the compensatory increase in the function of glandular cells under certain stress states. Poradovskaia et al. showed that after ablating or removing one submandibular salivary gland in rats, the contralateral gland responded by increasing cell proliferation with concomitant increases in the size of the cells and nuclei by 10% and 17%, respectively. Burlage et al. observed that pilocarpine preconditioning induced proliferation of acinar and intercalated duct cells in rats, which could explain the observed enhanced compensatory response in salivary glands [43]. Compensatory proliferation is a mechanism to replace lost cells in rapidly cycling tissues [44]. After an initial singular dose 131I dose of 100 mCi, the salivary glands might increase uptake to maintain secretory function [4]. Our results are consistent with those of the above-mentioned studies. It is believed that salivary glands with slight damage in the basal state have a certain compensatory function. After the initial radiation injury, the compensatory function of gland cells is activated by stress, manifesting as increased uptake or excretion. With the increase of radiation dose and the passage of time after 131I treatment, this compensatory function gradually decreases or disappears. In this study, we also selected uninjured salivary glands and compared the functional parameters before and after 131I therapy. Notably, these salivary glands were more likely to be affected than those that were already impaired before treatment. Most showed functional reduction without the phenomenon of functional compensatory increase. This provides new ideas for clinical treatment. For example, salivary gland protection should be strengthened during 131I treatment, especially in patients with normal basal function.

4.3. Different Glands

The salivary gland imaging results after the first and second 131I treatments showed that the submandibular glands are more sensitive than the parotid ones, and the most common change was a decreased UF value representing impaired uptake. We analyzed whether this difference was related to salivary gland cell characteristics and salivary gland structure. Damage to the microvascular endothelial cells in salivary glands caused by radiotherapy is one of the causes of impaired gland function [45, 46]. It leads to microvascular dysfunction and the production of ceramide and reactive oxygen species (ROS) that can induce gland dysfunction. ROS scavengers are used to protect salivary gland function in radiotherapy patients [47]. By inhibiting or eliminating aberrant oxidation reactions, it is possible to reduce damage to salivary gland function caused by radiation. One study found that levels of salivary non-enzymatic antioxidants and antioxidant enzymes in the saliva secreted by the parotid gland were higher than those secreted by the submandibular salivary glands [48]. Therefore, salivary gland function changes due to parotid microvascular injury are not as serious as those caused by submandibular microvascular injury. Another group showed that the saliva-to-serum 131I concentration rates in the parotid gland of mice and humans were 0.59 and 4.6, espectively, while those in the submandibular gland were 5.1 and 6.9 [49]. The 131I concentration was higher in the submandibular glands of both species. An investigation showed that murine duct cells in the different salivary glands varied greatly in their ability to concentrate iodide, so it could be shown that 131I was mainly concentrated in the ducts of the submandibular glands in mice, with lower levels in the parotid gland and very little in sublingual gland ducts [50]. Because of their ability to concentrate 131I, the submandibular glands are more susceptible to radiation damage.

After the first 131I treatment, we performed a second scintigraphy scan. We found that the males younger than 55 and females older than 55 showed a tendency of decreased function of the left parotid gland compared to the right parotid gland. The differential changes in the left and right glands after radiation have been reported in several studies and may be due to the asymmetric concentration of radioactive iodine in the salivary glands [3, 15, 31].

4.4. Treatment Frequency and 131I Dose

The Chi-square test showed that the difference between the number of damaged and undamaged salivary glands in males and females increased significantly with the increase of treatment times, and the percentage of damaged glands also increased gradually. The number of treatments was correlated with the 131I cumulative dose. A correlation between radiation dose and salivary gland dysfunction was previously reported [51, 52]. A salivary glandular scintillation imaging study showed that ∼30% of salivary parenchymal function was lost following a single 131I dose of 6 GBq (162 mCi), with a cumulative dose of 35 GBq (945 mCi) resulting in complete loss of glandular function [53]. Parthasarathy and Crawford argued that significant side effects were rarely seen at doses <3.7 GBq (100 mCi) [54].

5. Limitations

Our results should be considered in the context of some limitations. First, this was a retrospective study with no survey to assess patient symptoms and signs, so it was not possible to add more conditions (e.g., dry mouth, difficulty swallowing, loss of taste) for case screening. Second, there was a small number of patients, especially among the group treated more than four times, which limited our analysis of salivary gland function in patients with DTC treated for more than 2–3 years. Third, clinical parameters and test data of some patients were missing. Finally, the lack of significant findings in males maybe because they only accounted for 27% of the study cohort.

6. Conclusions

This study quantitatively compared salivary scintigraphy parameters in DTC patients after multiple 131I treatments. Salivary gland function sensitivities are quite variable in different ages and sexes, with the highest sensitivity in women younger than 55. After treatment, the uptake or secretion function of some salivary glands with impaired basic function increased. Decreased salivary gland function is significantly related to the number of 131I treatments and the cumulative dose. The parotid glands have the most significant reduction in uptake.

Acknowledgments

This work was supported by the National Natural Science Foundation of China grants (#81571709 and #81971650 to Zhaowei Meng, #81872169 to Xiangqian Zheng) and the design of this research was funded by the Key Project of Tianjin Science and Technology Committee Foundation grant (#16JCZDJC34300 to Zhaowei Meng), Tianjin Science and Technology Committee Foundation grants (#19JCYBJC27400 to Xiangqian Zheng), Tianjin Medical University General Hospital New Century Excellent Talent Program (to Zhaowei Meng), Young and Middle-aged Innovative Talent Training Program from Tianjin Education Committee (to Zhaowei Meng), and Talent Fostering Program (the 131 Project) from Tianjin Education Committee and Tianjin Human Resources and Social Security Bureau (to Zhaowei Meng).

Data Availability

The data generated in the study are included in this article. The database is available upon request.

Disclosure

XL and LY are co-first authors. ZM and YW are co-corresponding authors.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors' Contributions

XL and LY contributed equally to the study. ZM and YW contributed equally to the study.

Supplementary Materials

Supplementary Materials

Table S1 summarizes the number of patients, age distribution, and cumulative dose before one or more 131I treatments. Table S2: Chi-square test was performed to determine the relationship between the number of patients by sex and the impairment of salivary gland function before each 131I treatment. There was a statistical difference in the left submandibular gland injury count between sexes before the first treatment (p < 0.05). Figure S1: The percentage of damaged salivary glands increased with the number of treatments in both sexes. Figure S2: The cumulative dose of 131I received by patients over several treatments.

Click here for additional data file. (244.8KB, zip)

References

  • 1.Miller K. D., Nogueira L., Mariotto A. B., et al. Cancer treatment and survivorship statistics, CA: A Cancer Journal for Clinicians . 2019;69(5):363–385. doi: 10.3322/caac.21565. [DOI] [PubMed] [Google Scholar]
  • 2.Haugen B. R., Alexander E. K., Bible K. C., et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid . 2016;26(1):1–133. doi: 10.1089/thy.2015.0020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Upadhyaya A., Zhou P., Meng Z., et al. Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer. Nuclear Medicine Communications . 2017;38(11):891–903. doi: 10.1097/mnm.0000000000000727. [DOI] [PubMed] [Google Scholar]
  • 4.Upadhyaya A., Meng Z., Wang P., et al. Effects of first radioiodine ablation on functions of salivary glands in patients with differentiated thyroid cancer. Medicine . 2017;96(25):p. e7164. doi: 10.1097/md.0000000000007164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Chung J.-K., Youn H. W., Kang J. H., Lee H. Y., Kang K. W. Sodium iodide symporter and the radioiodine treatment of thyroid carcinoma. Nuclear Medicine and Molecular Imaging . 2010;44(1):4–14. doi: 10.1007/s13139-009-0016-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Badam R. K., Suram J., Babu D. B., et al. Assessment of salivary gland function using salivary scintigraphy in pre and post radioactive iodine therapy in diagnosed thyroid carcinoma patients. Journal of Clinical and Diagnostic Research: Journal of Clinical and Diagnostic Research . 2016;10 doi: 10.7860/JCDR/2016/16091.7121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.La Perle K. M. D., Kim D. C., Hall N. C., et al. Modulation of sodium/iodide symporter expression in the salivary gland. Thyroid . 2013;23(8):1029–1036. doi: 10.1089/thy.2012.0571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Llena-Puy C. The rôle of saliva in maintaining oral health and as an aid to diagnosis, Medicina Oral. Patología Oral y Cirugía Bucal. . 2006;11(5) [PubMed] [Google Scholar]
  • 9.Kaufman E., Lamster I. B., Lamster I. B. The diagnostic applications of saliva- A review. Critical Reviews in Oral Biology & Medicine . 2002;13(2):197–212. doi: 10.1177/154411130201300209. [DOI] [PubMed] [Google Scholar]
  • 10.Lenander-Lumikari M., Loimaranta V. Saliva and dental caries. Advances in Dental Research . 2000;14(1):40–47. doi: 10.1177/08959374000140010601. [DOI] [PubMed] [Google Scholar]
  • 11.Atkinson J. C., Grisius M., Massey W., Massey W. Salivary hypofunction and xerostomia: diagnosis and treatment. Dental Clinics of North America . 2005;49(2):309–326. doi: 10.1016/j.cden.2004.10.002. [DOI] [PubMed] [Google Scholar]
  • 12.Klein Hesselink E. N., Brouwers A. H., de Jong J. R., et al. Effects of radioiodine treatment on salivary gland function in patients with differentiated thyroid carcinoma: a prospective study. Journal of Nuclear Medicine . 2016;57(11):1685–1691. doi: 10.2967/jnumed.115.169888. [DOI] [PubMed] [Google Scholar]
  • 13.Solans R., Bosch J. A., Galofré P., et al. Salivary and lacrimal gland dysfunction (sicca syndrome) after radioiodine therapy. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine . 2001;42(5):738–743. [PubMed] [Google Scholar]
  • 14.Hyer S., Kong A., Pratt B., Harmer C., Harmer C. Clinical Oncology . 1. Vol. 19. (Royal College of Radiologists); 2007. Salivary gland toxicity after radioiodine therapy for thyroid cancer; pp. 83–86. [DOI] [PubMed] [Google Scholar]
  • 15.Wu J.-q., Feng H.-j., Ouyang W., et al. Systematic evaluation of salivary gland damage following I-131 therapy in differentiated thyroid cancer patients by quantitative scintigraphy and clinical follow-up. Nuclear Medicine Communications . 2015;36(8):819–826. doi: 10.1097/mnm.0000000000000325. [DOI] [PubMed] [Google Scholar]
  • 16.Horvath E., Skoknic V., Majlis S., et al. Radioiodine-induced salivary gland damage detected by ultrasonography in patients treated for papillary thyroid cancer: radioactive iodine activity and risk. Thyroid . 2020;30(11):1646–1655. doi: 10.1089/thy.2019.0563. [DOI] [PubMed] [Google Scholar]
  • 17.Muralidharan D., Fareed N., Pradeep P. V., et al. Qualitative and quantitative changes in saliva among patients with thyroid dysfunction prior to and following the treatment of the dysfunction. Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology . 2013;115(5):617–623. doi: 10.1016/j.oooo.2012.12.009. [DOI] [PubMed] [Google Scholar]
  • 18.Gupta T., Hotwani C., Kannan S., et al. Prospective longitudinal assessment of parotid gland function using dynamic quantitative pertechnate scintigraphy and estimation of dose-response relationship of parotid-sparing radiotherapy in head-neck cancers. Radiation Oncology . 2015;10(1):p. 67. doi: 10.1186/s13014-015-0371-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Aksoy T., Kiratli P. O., Erbas B., Erbas B. Correlations between histopathologic and scintigraphic parameters of salivary glands in patients with Sjögren’s syndrome. Clinical Rheumatology . 2012;31(9):1365–1370. doi: 10.1007/s10067-012-2024-2. [DOI] [PubMed] [Google Scholar]
  • 20.Anjos D. A., Etchebehere E. C. S. C., Santos A. O., et al. Normal values of [99mTc]pertechnetate uptake and excretion fraction by major salivary glands. Nuclear Medicine Communications . 2006;27(4):395–403. doi: 10.1097/01.mnm.0000202864.52046.b1. [DOI] [PubMed] [Google Scholar]
  • 21.Proctor G. B., Shaalan A. M., Shaalan A. M. Disease-induced changes in salivary gland function and the composition of saliva. Journal of Dental Research . 2021;100(11):1201–1209. doi: 10.1177/00220345211004842. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Barr J. Y., Wang X., Kreiger P. A., Lieberman S. M., Lieberman S. M. Salivary-gland-protective regulatory T-cell dysfunction underlies female-specific sialadenitis in the non-obese diabetic mouse model of Sjögren syndrome. Immunology . 2018;155(2):225–237. doi: 10.1111/imm.12948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Zhang Y. Q., Ye X., Meng Y., Zhao Y. N., Liu D. G., Yu G. Y. Evaluation of parotid gland function before and after endoscopy-assisted stone removal. Journal of Oral and Maxillofacial Surgery: Official Journal of the American Association of Oral and Maxillofacial Surgeons . 2019;77(2) doi: 10.1016/j.joms.2018.09.034. [DOI] [PubMed] [Google Scholar]
  • 24.Chern A., Famuyide A. O., Moonis G., Lalwani A. K., Lalwani A. K. Sialadenitis: a possible early manifestation of covid ‐19. The Laryngoscope . 2020;130(11):2595–2597. doi: 10.1002/lary.29083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Knaś M., Maciejczyk M., Sawicka K., et al. Impact of morbid obesity and bariatric surgery on antioxidant/oxidant balance of the unstimulated and stimulated human saliva. Journal of Oral Pathology & Medicine: Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology . 2016;45(6):455–464. doi: 10.1111/jop.12383. [DOI] [PubMed] [Google Scholar]
  • 26.Maciejczyk M., Matczuk J., Żendzian-Piotrowska M., et al. Eight-week consumption of high-sucrose diet has a pro-oxidant effect and alters the function of the salivary glands of rats. Nutrients . 2018;10(10) doi: 10.3390/nu10101530. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Choi J.-S., Park I. S., Kim S.-k., Lim J.-Y., Kim Y. M., Kim Y.-M. Analysis of age-related changes in the functional morphologies of salivary glands in mice. Archives of Oral Biology . 2013;58(11):1635–1642. doi: 10.1016/j.archoralbio.2013.07.008. [DOI] [PubMed] [Google Scholar]
  • 28.Pedersen W., Schubert M., Izutsu K., Mersai T., Truelove E., Truelove E. Clinical science age-dependent decreases in human submandibular gland flow rates as measured under resting and post-stimulation conditions. Journal of Dental Research . 1985;64(5):822–825. doi: 10.1177/00220345850640050801. [DOI] [PubMed] [Google Scholar]
  • 29.Lin L., Sijin L. Clinical guidelines for 131I treatment of Graves’ hyperthyoidism (2021 edition) Chinese Society of Nuclear Medicine . 2021;41(04):242–253. (in Chinese) [Google Scholar]
  • 30.Fallahi B., Beiki D., Abedi S. M., et al. Does vitamin E protect salivary glands from I-131 radiation damage in patients with thyroid cancer? Nuclear Medicine Communications . 2013;34(8):777–786. doi: 10.1097/mnm.0b013e328362b1f2. [DOI] [PubMed] [Google Scholar]
  • 31.An Y.-S., Yoon J.-K., Lee S. J., et al. Symptomatic late-onset sialadenitis after radioiodine therapy in thyroid cancer. Annals of Nuclear Medicine . 2013;27(4):386–391. doi: 10.1007/s12149-013-0697-5. [DOI] [PubMed] [Google Scholar]
  • 32.Shizukuishi K., Nagaoka S., Kinno Y., et al. Scoring analysis of salivary gland scintigraphy in patients with Sjögren’s syndrome. Annals of Nuclear Medicine . 2003;17(8):627–631. doi: 10.1007/bf02984967. [DOI] [PubMed] [Google Scholar]
  • 33.Roesink J. M., Moerland M. A., Hoekstra A., Rijk P. P. V., Terhaard C. H., Terhaard C. H. J. Scintigraphic assessment of early and late parotid gland function after radiotherapy for head-and-neck cancer: a prospective study of dose-volume response relationships. International Journal of Radiation Oncology, Biology, Physics . 2004;58(5):1451–1460. doi: 10.1016/j.ijrobp.2003.09.021. [DOI] [PubMed] [Google Scholar]
  • 34.Sunavala-Dossabhoy G. Radioactive iodine: an unappreciated threat to salivary gland function. Oral Diseases . 2018;24(1-2):198–201. doi: 10.1111/odi.12774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Caglar M., Tuncel M., Alpar R., Alpar R. Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment. Clinical Nuclear Medicine . 2002;27(11):767–771. doi: 10.1097/00003072-200211000-00003. [DOI] [PubMed] [Google Scholar]
  • 36.Jo K. S., An Y.-S., Lee S. J., et al. Significance of salivary gland radioiodine retention on post-ablation 131I scintigraphy as a predictor of salivary gland dysfunction in patients with differentiated thyroid carcinoma. Nuclear Medicine and Molecular Imaging . 2014;48(3):203–211. doi: 10.1007/s13139-014-0274-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Liu B., Huang R., Kuang A., et al. Iodine kinetics and dosimetry in the salivary glands during repeated courses of radioiodine therapy for thyroid cancer. Medical Physics . 2011;38(10):5412–5419. doi: 10.1118/1.3602459. [DOI] [PubMed] [Google Scholar]
  • 38.Almeida J. P., Sanabria Á. E., Lima E. N. P., Kowalski L. P., Kowalski L. P. Late side effects of radioactive iodine on salivary gland function in patients with thyroid cancer. Head & Neck . 2011;33(5):686–690. doi: 10.1002/hed.21520. [DOI] [PubMed] [Google Scholar]
  • 39.Levi-Montalcini R., Cohen S. Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals. Annals of the New York Academy of Sciences . 1960;85:324–341. doi: 10.1111/j.1749-6632.1960.tb49963.x. [DOI] [PubMed] [Google Scholar]
  • 40.Byyny R. L., Orth D. N., Cohen S., Doyne E. S. Epidermal growth factor: effects of androgens and adrenergic agents. Endocrinology . 1974;95(3):776–82. doi: 10.1210/endo-95-3-776. [DOI] [PubMed] [Google Scholar]
  • 41.Ishii D. N., Shooter E. M. Regulation of nerve growth factor synthesis in mouse submaxillary glands by testosterone. Journal of Neurochemistry . 1975;25(68):43–51. doi: 10.1111/j.1471-4159.1975.tb04416.x. [DOI] [PubMed] [Google Scholar]
  • 42.Brandt J. E., Priori R., Valesini G., Fairweather D. Sex differences in Sjögren’s syndrome: a comprehensive review of immune mechanisms. Biology of Sex Differences . 2015;6:p. 19. doi: 10.1369/0022155420922948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Burlage F. R., Faber H., Kampinga H. H., Langendijk J. A., Vissink A., Coppes R. P. Enhanced proliferation of acinar and progenitor cells by prophylactic pilocarpine treatment underlies the observed amelioration of radiation injury to parotid glands. Radiotherapy & Oncology . 2009;90(2):253–256. doi: 10.1016/j.radonc.2008.11.011. [DOI] [PubMed] [Google Scholar]
  • 44.Denekamp J. Cell kinetics and radiation biology. International Journal of Radiation Biology & Related Studies in Physics, Chemistry & Medicine . 1986;49(2):357–380. doi: 10.1080/09553008514552591. [DOI] [PubMed] [Google Scholar]
  • 45.Cotrim A. P., Sowers A., Mitchell J. B., Baum B. J., Baum B. J. Prevention of irradiation-induced salivary hypofunction by microvessel protection in mouse salivary glands. Molecular Therapy . 2007;15(12):2101–2106. doi: 10.1038/sj.mt.6300296. [DOI] [PubMed] [Google Scholar]
  • 46.Zhang Z., Cui F., Cao C., Wang Q., Zou Q. Single-cell RNA analysis reveals the potential risk of organ-specific cell types vulnerable to SARS-CoV-2 infections. Computers in Biology and Medicine . 2022;140 doi: 10.1016/j.compbiomed.2021.105092.105092 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Mizrachi A., Cotrim A. P., Katabi N., et al. Radiation-induced microvascular injury as a mechanism of salivary gland hypofunction and potential target for radioprotectors. Radiation Research . 2016;186(2):189–195. doi: 10.1667/rr14431.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Błochowiak K., Witmanowski H. Ocena stężenia produktów peroksydacji lipidów w ślinie i w surowicy krwi u pacjentów ze złamaniami żuchwy. Czasopismo Stomatologiczne . 2010;63(4):250–258. [Google Scholar]
  • 49.Cohen B., Myant N. B., Myant N. B. Concentration of salivary iodide: a comparative study. The Journal of Physiology . 1959;145(3):595–610. doi: 10.1113/jphysiol.1959.sp006165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Logothetopoulos J. H., Myant N. B., Myant N. B. Concentration of radio-iodide and 35-S-thiocyanate by the salivary glands. The Journal of Physiology . 1956;134(1):189–194. doi: 10.1113/jphysiol.1956.sp005634. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 51.Solans R., Bosch J. A., Galofré P., et al. Salivary and lacrimal gland dysfunction (Sicca syndrome) after radioiodine therapy. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine . 2001;42:738–743. [PubMed] [Google Scholar]
  • 52.Alexander C., Bader J. B., Schaefer A., Finke C., Kirsch C. M. Intermediate and long-term side effects of high-dose radioiodine therapy for thyroid carcinoma. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine . 1998;39(9):1551–1554. [PubMed] [Google Scholar]
  • 53.Jentzen W., Schneider E., Freudenberg L., et al. Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer. Nuclear Medicine Communications . 2006;27(8):669–676. doi: 10.1097/00006231-200608000-00009. [DOI] [PubMed] [Google Scholar]
  • 54.Parthasarathy K. L., Crawford E. S. Treatment of thyroid carcinoma: emphasis on high-dose 131I outpatient therapy. Journal of Nuclear Medicine Technology . 2002;30(4):165–173. quiz 172-3. [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Materials

Table S1 summarizes the number of patients, age distribution, and cumulative dose before one or more 131I treatments. Table S2: Chi-square test was performed to determine the relationship between the number of patients by sex and the impairment of salivary gland function before each 131I treatment. There was a statistical difference in the left submandibular gland injury count between sexes before the first treatment (p < 0.05). Figure S1: The percentage of damaged salivary glands increased with the number of treatments in both sexes. Figure S2: The cumulative dose of 131I received by patients over several treatments.

Click here for additional data file. (244.8KB, zip)

Data Availability Statement

The data generated in the study are included in this article. The database is available upon request.

Articles from Journal of Healthcare Engineering are provided here courtesy of Wiley

RESOURCES