Does lemon candy decrease salivary gland damage after radioiodine therapy for thyroid cancer?

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.     

131I致分化型甲状腺癌患者唾液腺辐射损伤及其防治的研究进展

131I治疗分化型甲状腺癌（DTC）的技术成熟、效果显著,是DTC患者术后综合治疗的主要方法之一,目前已被广泛应用于临床。但其造成的唾液腺辐射损伤（口干、腮腺肿痛、味觉改变等）会对DTC患者的生活质量造成一定影响。近年来,各种唾液腺辐射损伤防护剂层出不穷,但其确切疗效较为局限,且治疗方案尚未规范统一。笔者就DTC患者术后行131I治疗对唾液腺的辐射损伤及其防治的研究进展进行综述。     

Amifostine is a Potent Radioprotector of Salivary Glands in Radioiodine Therapy

BACKGROUND AND PURPOSE: Salivary gland impairment following high-dose radioiodine treatment is well recognized. Since differentiated thyroid cancer has a good prognosis, reduction of long-term side effects is important. This study investigates the radioprotective effects of amifostine in salivary glands of rabbits receiving high-dose radioiodine therapy so as to obtain deeper insight in changes on the cellular and ultrastructural level. MATERIAL AND METHODS: A total of 20 rabbits were investigated. High-dose radioiodine therapy applying 1 GBq (131)I was performed in 16 animals. Eight of these 16 animals received 200 mg/m(2) body surface amifostine prior to high-dose radioiodine therapy. Four additional rabbits served as controls, two receiving amifostine, the other two no treatment at all. Subsequently, salivary glands (submandibular and parotid glands, respectively) of all animals were examined by light and transmission electron microscopy. RESULTS: Parenchymal damage of both parotid and submandibular glands, specially acinar structures comprising cell organelles and nuclei, of animals pretreated with amifostine was much less pronounced than in animals without amifostine pretreatment. CONCLUSION: The results indicate that parenchymal damage in salivary glands induced by high-dose radioiodine therapy can significantly be reduced by amifostine. Therefore, amifostine therapy may increase quality of life in patients with differentiated thyroid cancer after radioiodine treatment.     

Proton therapy for tumors of the skull base

BACKGROUND: Salivary gland impairment following high-dose radioiodine treatment is a well-recognized side effect, in general caused by free radicals. Therefore, it seemed promising to evaluate the radioprotective effect of the radical scavenger amifostine in patients receiving high-dose radioiodine therapy. PATIENTS AND METHOD: Quantitative salivary gland scintigraphy using 100 to 120 MBq Tc-99m-pertechnetate was performed in 17 patients with differentiated thyroid cancer prior to and 3 months after radioiodine treatment with 6 GBq I-131. Eight patients were treated with 500 mg/m2 amifostine prior to high-dose radioiodine treatment and compared retrospectively with 9 control patients. Xerostomia was graded according to WHO criteria. RESULTS: In 9 control patients high-dose radioiodine treatment significantly (p < 0.01) reduced Tc-99m-pertechnetate uptake by 35.4 +/- 22.0% and 31.7 +/- 21.1% in parotid and submandibular glands, respectively. Of these 9 patients, 3 exhibited xerostomia Grade I (WHO). In contrast, in 8 amifostine-treated patients, there was no significant (p = 0.878) decrease in parenchymal function following high-dose radioiodine treatment, and xerostomia did not occur in any of them. CONCLUSION: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be reduced significantly by amifostine. This may help to increase patients' quality of life in differentiated thyroid cancer.     

Side effects of "rational dose" iodine-131 therapy for metastatic well-differentiated thyroid carcinoma

Benua, Leeper, and others (BEL) have advocated the estimation of radiation exposure to the blood to select a more rational maximum safe dose of radioiodine (dosimetry) to treat metastatic functioning well-differentiated thyroid carcinoma. After adopting the BEL dosimetry approach, we reviewed the immediate (during hospitalization) and intermediate (from discharge up to 3 mo) side effects after our initial 15 therapies in ten patients. The doses ranged from 51 mCi (1,887 MBq) to 450 mCi (16.65 GBq). Immediate side effects were observed in 12/15 (80%), are described in detail, and were as follows: gastrointestinal 10/15, salivary 9/15, nonsalivary neck pain, swelling, etc. 2/15, pulmonary 0/15. Intermediate side effects were observed in 10/15 (67%), are described in detail, and were as follows: gastrointestinal 0/15, salivary 3/15, nonsalivary neck pain, swelling, etc. 3/15, nasal complaints 2/15, transient bone marrow suppression 9/10, pulmonary 0/15. No patient required blood transfusions or had complications secondary to reduced blood counts. All patient complaints resolved; however, several patients may have reduced baseline blood counts one year after therapy. No other long-term side effect has been noted but the mean follow-up has been only 15 mo. In our opinion, we have not observed any side effect to date which would contraindicate the continued use and evaluation of the BEL dosimetry approach.     

Semi-quantitative assessment of salivary gland function in patients with differentiated thyroid carcinoma after radioiodine-131 treatment

Sialadenitis and xerostomia are well-known side effects of high-dose radioactive iodine ((131)Iota) treatment in patients with differentiated thyroid carcinoma (DTC). This study was undertaken to determine salivary gland function semi-quantitatively in patients with DTC given (131)I for the treatment of the thyroid remnant and/or metastases. Thirty-six patients, 11 males and 25 females, mean age 53.5 years, range 22-73 years, were studied. Scintigraphy of the salivary glands was performed with (99m)Tc-pertechnetate and the salivary excretion fraction (SEF) of the parotid and the submandibular glands was calculated as a measure of their function. Measurements were performed before (131)I treatment as a baseline study, and three weeks and three months later. The patients were clinically evaluated by a standardized subjective questionnaire. Results were as follows: Mean SEF at three weeks and three months after (131)I treatment was reduced as compared to baseline measurements. The total mean baseline measurements, those of three weeks and those of three months later were: 54.9%, 47.2% and 46% respectively; P<0.05 for both measurements (Table 1). The SEF decrease of the parotid glands was greater than that of the submandibular glands (P<0.05 as compared for both salivary glands before and three weeks and three months after (131)I treatment). This confirmed the higher radiosensitivity of the parotid glands as compared to the submandibular glands. In 12 patients (33%) there was no significant decrease of SEF in the salivary glands after (131)I treatment. The relation between the decrease of SEF after three weeks and after three months and the dose of (131)I administered, was for the right and left submandibular glands significant (P=0.016 and P=0.002), while for the parotid glands it was insignificant (P=0.22 and P=0.27 respectively) (Table 4). Reduction of SEF in the parotid glands three months after (131)I treatment was greater than after three weeks. This difference, as regards the submandibular glands, was not significant. Our results show that high dose (131)I treatment in DTC patients induces a significant effect on salivary gland function, which is dose-related in the submandibular glands, and more prominent in the parotid glands.     

RETRACTED ARTICLE: Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

Radioactive iodine (¹³¹I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, ¹³¹I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the ¹³¹I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of ¹³¹I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of ¹³¹I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with ¹³¹I-induced sialadenitis that is unresponsive to medical treatment.     

Relationship between cumulative radiation dose and salivary gland uptake associated with radioiodine therapy of thyroid cancer

AIM: To estimate the individual absorbed dose to the parotid and submandibular salivary glands in radioiodine therapy and its dependence from the previous cumulative therapy. METHODS: Fifty-five patients with differentiated thyroid carcinoma after thyroidectomy received 1-21 GBq (131)I using single activities of 1-6 GBq. The patients were stratified according to the cumulative activities into low-activity (1-2 GBq), middle-activity (3-7 GBq), and high-activity groups (9-21 GBq). The time-activity curves over the respective salivary glands were derived from multiple static calibrated images measured for each patient up to 48 h after ingestion of the radioiodine therapy capsule with a gamma camera. Manually drawn regions of interests were used to determine the background activities and the activities arising from the salivary glands. The gland volumes were determined by ultrasonography using appropriate volume models. RESULTS: The median absorbed dose per administered activity of each single parotid and submandibular gland was about 0.15 Gy.GBq (range, 0.1-0.3 Gy.GBq(-1)) and 0.48 Gy.GBq(-1) (range, 0.2-1.2 Gy.GBq(-1)), respectively. The maximum uptake of both gland types was significantly lower for the high-activity than for the low-activity groups and correlated with the mean cumulative administered activity of the activity groups. CONCLUSION: The iodine uptake of salivary glands is significantly reduced, whereas the absorbed dose per administered (131)I activity was not significantly decreased during the course of therapy. Comparing the well-known dose-effect relationships in external radiation therapy, the absorbed dose per administered (131)I activity is too low to induce comparable radiation damage, suggesting an inhomogeneous distribution of (131)I in human salivary glands.     

The influence of saliva flow stimulation on the absorbed radiation dose to the salivary glands during radioiodine therapy of thyroid cancer using 124I PET(/CT) imaging

Purpose

A serious side effect of high-activity radioiodine therapy in the treatment of differentiated thyroid cancer is radiogenic salivary gland damage. This damage may be diminished by lemon-juice-induced saliva flow immediately after ¹³¹I administration. The aim of this study was to assess the effect of chewing lemon slices on the absorbed (radiation) doses to the salivary glands.

Methods

Ten patients received (pretherapy) ¹²⁴I PET(/CT) dosimetry before their first radioiodine therapy. The patients underwent a series of six PET scans at 0.5, 1, 2, 4, 48 and ≥96 h and one PET/CT scan at 24 h after administration of 27 MBq ¹²⁴I. Blood samples were also collected at about 2, 4, 24, 48, and 96 h. Contrary to the standard radioiodine therapy protocol, the patients were not stimulated with lemon juice. Specifically, the patients chewed no lemon slices during the pretherapy procedure and neither ate food nor drank fluids until after completion of the last PET scan on the first day. Organ absorbed doses per administered ¹³¹I activity (ODpAs) as well as gland and blood uptake curves were determined and compared with published data from a control patient group, i.e. stimulated per the standard radioiodine therapy protocol. The calculations for both groups used the same methodology.

Results

A within-group comparison showed that the mean ODpA for the submandibular glands was not significantly different from that for the parotid glands. An intergroup comparison showed that the mean ODpA in the nonstimulation group averaged over both gland types was reduced by 28% compared to the mean ODpA in the stimulation group (p=0.01). Within each gland type, the mean ODpA reductions in the nonstimulation group were statistically significant for the parotid glands (p=0.03) but not for the submandibular glands (p=0.23). The observed ODpAs were higher in the stimulation group because of increased initial gland uptake rather than group differences in blood kinetics.

Conclusion

The ¹²⁴I PET(/CT) salivary gland dosimetry indicated that lemon juice stimulation shortly after ¹³¹I administration in radioiodine therapy increases the absorbed doses to the salivary glands.     

Prostaglandins as biochemical markers of radiation injury to the salivary glands after iodine-131 therapy?

Because salivary glands, as well as thyroid tissue, are able to concentrate radioiodine, the treatment of thyroid diseases with iodine-131 may have secondary effects on salivary gland function which seriously impair the quality of life. Such effects include sialoadenitis and xerostomia. Salivary secretion is stimulated by prosta- glandins (PGs). In this study we evaluate whether ¹³¹I therapy influences the levels of PGs in saliva. Patients who had previously received ¹³¹I for treatment of hyperthyroidism or differentiated thyroid cancer and healthy volunteers were studied. Levels of PGs [6-oxo-PGF_1α, bicyclo-PGEm, thromboxane B₂ (TXB₂), PGF_2α] in unstimulated saliva were measured using enzyme immunoassay. Significantly lower levels of 6-oxo-PGF_1α, bicyclo-PGEm and PGF_2α and higher levels of TXB₂ were found in the group of patients in comparison with the controls. Differences between patients and controls were more pronounced in smokers. This study demonstrates that salivary gland uptake of ¹³¹I significantly affects PG levels in saliva. Received 25 September and in revised form 24 November 1997     

Significance of Salivary Gland Radioiodine Retention on Post-ablation 131I Scintigraphy as a Predictor of Salivary Gland Dysfunction in Patients with Differentiated Thyroid Carcinoma

Purpose

We investigated whether ¹³¹I whole-body scintigraphy could predict functional changes in salivary glands after radioiodine therapy.

Methods

We evaluated 90 patients who received initial high-dose (≥3.7 GBq) radioiodine therapy after total thyroidectomy. All patients underwent diagnostic (DWS) and post-ablation (TWS) ¹³¹I whole-body scintigraphy. Visual assessment of salivary radioiodine retention on DWS and TWS was used to divide the patients into two types of groups: a DWS+ or DWS- group and a TWS+ or TWS- group. Salivary gland scintigraphy was also performed before DWS and at the first follow-up visit. Peak uptake and %washout were calculated in ROIs of each gland. Functional changes (Δuptake or Δwashout) of salivary glands after radioiodine therapy were compared between the two groups.

Results

Both peak uptake and the %washout of the parotid glands were significantly lower after radioiodine therapy (all p values <0.001), whereas only the %washout were significantly reduced in the submandibular glands (all p values <0.05). For the parotid glands, the TWS+ group showed larger Δuptake and Δwashout after radioiodine therapy than did the TWS- group (all p values <0.01). In contrast, the Δuptake and Δwashout of the submandibular glands did not significantly differ between the TWS+ and TWS- groups (all p values >0.05). Likewise, no differences in Δuptake or Δwashout were apparent between the DWS+ and DWS- groups in either the parotid or submandibular glands (all p values >0.05).

Conclusion

Salivary gland radioiodine retention on post-ablation ¹³¹I scintigraphy is a good predictor of functional impairment of the parotid glands after high-dose radioiodine therapy.     

Thyroglobulin and 131I uptake of remaining tissue in patients with differentiated carcinoma after thyroidectomy

In 158 thyroidectomized patients with well-differentiated non-metastatic thyroid cancer the results of serum thyroglobulin (Tg) determination and 131I uptake values established immediately before radioiodine treatment (19 days after surgery) were compared. In 113 patients (72%) Tg was above 6 ng ml-1 (lower limit of detection) and 131I uptake exceeded 2%. In 11 patients (7%) Tg was undetectable and 131I uptake less than 2%. In these cases a radioiodine treatment was not performed; the thyroid ablation was achieved by surgery only. In 34 patients (21%) with undetectable Tg, 131I uptake values, however, varied between 3 and 46% (mean value: 9.6%). Only in 4 of these 34 patients was TSH not maximally (50 microU ml-1) stimulated because of a shorter (9, 10, 11, 13 days) period from thyroidectomy. In conclusion, remaining thyroid tissue, highly stimulated by TSH, can trap a remarkable amount of radioiodine, but may be unable to produce detectable amounts of Tg. Therefore, in contrast to 131I, measuring Tg is insufficient to document the success of thyroid ablation. For the first follow-up study after ablative therapy, the uptake test with radioiodine is mandatory.     

Pre-therapeutic 124I PET(/CT) dosimetry confirms low average absorbed doses per administered 131I activity to the salivary glands in radioiodine therapy of differentiated thyroid cancer

Purpose  

Salivary gland impairment following high activity radioiodine therapy of differentiated thyroid cancer (DTC) is a severe side effect. Dosimetric calculations using planar gamma camera scintigraphy (GCS) with ¹³¹I and ultrasonography (US) provided evidence that the average organ dose per administered ¹³¹I activity (ODpA) is too low to account for observed radiation damages to the salivary glands. The objective of this work was to re-estimate the ODpA using ¹²⁴I PET(/CT) as a more reliable approach than ¹³¹I GCS/US.     

The sodium-iodine symporter and the proton-pump inhibitors in - related to the side effects of- the treatment of thyroid cancer with iodine-131

Iodine-131 ((131)I) administered to patients for imaging or treatment, concentrates in the gastrointestinal tract, including the salivary glands, stomach and bowel. In Nuclear Medicine practice this biological property of iodine causes side effects when the therapeutic dose of (131)I is large. This occurs during the treatment of patients with differentiated thyroid carcinoma (DTC). During this clinical application, the dose of (131)I is higher than 3.7 GBq. Side effects of this treatment with respect to the stomach, include gastritis as an inflammatory reaction to radiation, anorexia due to gastric atrophy and rarely megaloblastic anemia due to lack of the endogenous factor. Side effects can also include xerostomia. We have recently tried to prevent gastric side effects by prescribing proton pump inhibitors (PPI) for patients with DTC prior to treatment with (131)I. PPI block the excretion of hydrochloric acid from the gastric mucosa and are utilized for the prevention and treatment of gastritis, gastric ulcers and gastroesophageal reflux. Whole body scans before or after the administration of PPI, showed that PPI do not interfere with the biologic distribution of (131)I. These findings were not surprising. Recent studies in animals and humans have shown that the accumulation and concentration of iodine by the thyroid gland is the result of the selective action of sodium iodine symporter (Na+I+symporter, NIS). Furthermore, it was shown that the accumulation and concentration of (131)I in the parietal cells of the gastric mucosa, the ductal cells of the salivary glands and the alveolar epithelial cells of the mammary glands, is analogous to the biologic action of NIS in the thyroid cells. The gastric mucosa accumulates iodine from the capillaries via the extracellular/extravascular space and finally excretes it into the lumen of the stomach, from where it is passively transferred into the bowel, where it is partially reabsorbed to once again enter its metabolic cycle. On the contrary, as it is now known, the PPI have an entirely different metabolic action, which is unrelated to that of the NIS, although both mechanisms coexist in the parietal cells of the gastric mucosa. Thus, during the application of (131)I for imaging or for the treatment of DTC patients, except for the short period of time immediately after the oral administration, when the radionuclide passes through the stomach, the concentration of (131)I in the gastrointestinal tract is due to its active accumulation and excretion by the gastric mucosa. PPI act only on the hydrochloric acid secretion not affecting the biologic properties of iodine.     

Scintigraphic evaluation of salivary gland dysfunction in patients with thyroid cancer after radioiodine treatment

PURPOSE: Sialadenitis is a well-recognized adverse effect of high-dose radioactive iodine treatment. This study was undertaken to determine whether Tc-99m pertechnetate salivary gland scintigraphy may be used for objective assessment of salivary gland function in patients with thyroid cancer treated with I-131. PATIENTS AND METHODS: The study group consisted of 71 patients (16 men, 55 women) with a mean age of 44 years (range, 16 to 73 years). Twenty-six (37%) patients were not given any radioiodine, and 18, 16, and 11 patients received doses of 100, 150, or 200 mCi (or higher), respectively. Parotid and submandibular glands were evaluated based on a four-grade scoring system. Correlation between the type of surgery, administered dose, time since therapy, subjective symptoms, and findings of salivary gland scintigraphy were evaluated. RESULTS: Subjective symptoms were questioned in 39 of the 45 patients who received radioactive iodine treatment. Fifty-four percent (21 of 39) of the patients reported xerostomia, of whom 86% (18 of 21) showed salivary gland dysfunction. Objective salivary gland dysfunction was observed in 69% (31 of 45) of patients. In 81% of the patients, the parotid glands were affected; in 13% of the patients, the submandibular glands were affected; and in 6%, both were affected ( < 0.000001). The frequency of salivary gland dysfunction showed a dose dependence to cumulative activity ( = 0.007). A greater complication rate was observed in patients with total thyroidectomy compared with subtotal surgery, although the correlation was not significant ( = 0.625). CONCLUSIONS: Parenchymal damage to the salivary glands induced by radioactive iodine treatment can be evaluated by salivary gland scintigraphy. The impairment is worse in the parotid glands and increases with the total dose.     

rhTSH stimulation before radioiodine therapy in thyroid cancer reduces the effective half-life of (131)I.

Recombinant human thyroid-stimulating hormone (rhTSH) is effectively used for exogenous thyroid-stimulating hormone (TSH) stimulation before diagnostic (131)I scintigraphy. It is not yet widely used for preparation of patients receiving a therapeutic amount of radioiodine. METHODS: The results of 64 consecutive therapeutic applications of rhTSH with regard to clinical tolerance and side effects were evaluated in comparison with 163 radioiodine therapies (RITs) done on patients with hypothyroidism after thyroxine withdrawal during the same period. All therapies-applying 1.1-10 GBq of (131)I-used a standardized protocol of patient preparation and activity application. RITs were followed by daily whole-body uptake measurements for 2-6 d, and a biexponential curve fit was used to obtain a short initial and afterward a long effective half-life of (131)I. Patients after rhTSH were evaluated as a whole group (group A, n = 64) and as a subset of that group with normal thyroglobulin (hTG) levels (group D, n = 18). Patients after endogenous TSH stimulation were evaluated as a whole group (group B, n = 163), as a subset of that group excluding all ablative RITs (group C, n = 113), and as a subset of that subset with normal hTG levels (group E, n = 87). RESULTS: rhTSH-stimulated patients showed significantly higher TSH values than did endogenously stimulated patients (P < 0.001). Furthermore, the effective half-life of (131)I was significantly prolonged after endogenous stimulation (e.g., 0.43 d for group A vs. 0. 54 d for group B, P < 0.001). All rhTSH applications were tolerated well and without serious side effects. The only side effects were 2 cases of nausea and headache. CONCLUSION: The use of rhTSH for stimulation of TSH before RIT is safe but also significantly reduces the effective half-life of (131)I. This is mainly due to a reduced renal iodine clearance in the hypothyroid state, but the bioavailability of radioiodine may be slightly overestimated because of larger amounts of intestinal (131)I after endogenous TSH stimulation.     

Radioiodine therapy induces dose-dependent in vivo oxidation injury: evidence by increased isoprostane 8-epi-PGF(2 alpha).

131I is the treatment of choice for differentiated thyroid cancer and hyperthyroidism. A relationship between low-density lipoprotein oxidation and radioiodine therapy-related side effects, consequently inducing increased formation of 8-epi-prostaglandin F(2 alpha) (PGF(2 alpha)) in situ, has recently been reported by several investigators. Isoprostanes, among them 8-epi-PGF(2 alpha), have been associated with increased oxidation injury due to various pathologic conditions in vivo. The aim of this study was to investigate the possible induction of oxidative stress as a consequence of (131)I therapy. METHODS: 8-epi-PGF(2 alpha) was examined in plasma, serum, and urine in 42 patients undergoing radioiodine treatment of hyperthyroidism or thyroid cancer. The 8-epi-PGF(2 alpha) levels were analyzed daily for 1 wk and thereafter at different points up to 12 wk after treatment. RESULTS: The isoprostane levels showed an increase after application of radioiodine in all investigated compartments. The effect was significantly higher and longer lasting after higher-activity therapy (2,960 or 7,400 MBq) than after lower-activity therapy (185 or 740 MBq). CONCLUSION: These findings document a significant, dose-dependent in vivo oxidation injury as a consequence of therapeutic radioiodine application to the salivary gland.     

Recombinant human thyrotropin (rhTSH) in the management of differentiated thyroid cancer

Recombinant human thyrotropin (rhTSH) has been evaluated in 38 patients with differentiated thyroid cancer. The patients had all been treated previously by operation and 31 had received radioiodine 131I. The patients continued to take thyroid hormone and changed to a low iodine diet for 14 days before and throughout the week of testing. The rhTSH was injected intramuscularly on two consecutive days, 74 MBq 131I was administered on the next day and scintigraphy completed 48 h after that. TSH was measured before administration of 131I, and thyroglobulin after the scan. All patients preferred this method to withdrawal of thyroid hormone, but 45% had mild symptoms including headache and nausea. The average TSH was 127 mU x l(-1), and was inversely related to the weight of the patients. Thirty-four had negative scans with a mean uptake of 0.06%. Thyroglobulin values above 10 ng x ml(-1) were found in seven patients, of whom four had similar findings when scanned after withdrawal of thyroid hormone. Of four with positive scans, two had undetectable thyroglobulin. The rate of clearance of 131I was compared in patients studied at 72 h who were hypothyroid and at 48 h in euthyroid patients given rhTSH and was found to be longer in the latter. We conclude that rhTSH can be used to stimulate thyroid tissue to trap 131I and secrete thyroglobulin. Both scan and thyroglobulin should be obtained. The method is well tolerated.     

综合干预措施下评估首次131I清甲治疗对分化型甲状腺癌患者唾液腺的慢性损伤

目的研究探讨分化型甲状腺癌（DTC）患者在采取综合干预措施后首次131I清甲治疗对唾液腺功能的慢性损伤情况。方法选取2016年8月至2017年9月在攀枝花市中心医院核医学科首次行131I（4200.24±604.21）MBq清甲治疗的DTC患者52例,所有患者均在131I清甲治疗后立即采取综合干预措施（饮食护理、心理护理、物理护理、口腔卫生护理、健康宣教及药物治疗等）,并分别于131I清甲前和治疗后6个月行99TcmO₄-唾液腺动态显像,计算其摄取峰值和排泌分数,所得数据采用自身配对t检验分析,同时联合口干评分法评估唾液腺功能的损伤情况。结果（1）左侧腮腺摄取峰值在131I清甲前为45.157±19.421,治疗后6个月为52.600±21.716,差异有统计学意义（t=2.470,P=0.018）。（2）右侧腮腺、双侧颌下腺的摄取峰值及双侧腮腺、双侧颌下腺的排泌分数之间的差异均无统计学意义（t=0.784、0.524、0.514、0.362、0.731、0.596、0.507,均P>0.05）。（3）对52例患者行问卷调查和口干评分法分析,其中,50例（96.2%）患者无口干症状,仅有2例（3.8%）出现轻度口干症状。结论（1）首次131I清甲治疗可引起DTC患者唾液腺功能受损,损伤主要以单侧腮腺摄取功能为主,呈非对称性损伤。双侧颌下腺的摄取和排泌功能则未受到明显影响。（2）症状上,在综合干预保护措施下,绝大部分患者在接受首次131I清甲治疗后6个月无明显口干情况,生活质量无明显影响。     

Procedure guidelines for radioiodine therapy of differentiated thyroid cancer (version 3)

The procedure guideline for radioiodine therapy (RIT) of differentiated thyroid cancer (version 3) is the counterpart to the procedure guideline for (131)I whole-body scintigraphy (version 3) and specify the interdisciplinary guideline for thyroid cancer of the Deutsche Krebsgesellschaft concerning the nuclear medicine part. Recommendation for ablative (131)I therapy is given for all differentiated thyroid carcinoma (DTC) >1 cm. Regarding DTC < or =1 cm (131)I ablation may be helpful in an individual constellation. Preparation for (131)I ablation requires low iodine diet for two weeks and TSH-stimulation by withdrawal of thyroid hormone medication or by use of recombinant human TSH (rhTSH). The advantages of rhTSH (no symptoms of hypothyroidism, lower blood activity) and the advantages of endogenous TSH-stimulation (necessary for (131)I-therapy in patients with metastases, higher sensitivity of (131)I whole-body scan) are discussed. In most centers standard activities are used for (131)I ablation. If pretherapeutic dosimetry is planned, the diagnostic administration of (131)I should not exceed 1-10 MBq, alternative tracers are (123)I or (124)I. The recommendations for contraception and family planning are harmonized with the recommendation of ATA and ETA. Regarding the best possible protection of salivary glands the evidence is insufficient to recommend a specific setting. To minimize the risk of dental caries due to xerostomia patients should use preventive strategies for dental hygiene.